Coordinate Actions of Growth Factors in Monocytes/Macrophages

  • C. F. Nathan
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 95 / 2)


A proposal to review the known actions of peptide growth factors on mononuclear phagocytes runs immediately into the obstacle of specifying which cytokines ought to be considered peptide growth factors. At this juncture, it is difficult even to define “cytokine.” Cytokine research is in transition. A flood of new facts has swept away old concepts; new ideas have not yet arisen with the power to reveal the logical relations among recent discoveries or predict the next ones. Thus, it seems necessary to explain the philosophical perspective from which this review has been written.


Visceral Leishmaniasis Chronic Granulomatous Disease Mononuclear Phagocyte Reactive Oxygen Intermediate Coordinate Action 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams DO, Hamilton TA (1987) Molecular transduction mechanisms by which interferon gamma and other signals regulate macrophage development. Immunol Rev 97: 5–28PubMedGoogle Scholar
  2. Adams DO, Johnson WJ, Fiorito E, Nathan CF (1981) Hydrogen peroxide and cytolytic factor can interact in effecting cytolysis of neoplastic targets. J Immunol 127: 1973–1977PubMedGoogle Scholar
  3. Adams JS, Gacod MA (1985) Characterization of 1-a-hydroxylase of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis. J Exp Med 161: 755–765PubMedGoogle Scholar
  4. Akagawa KS, Tokunaga T (1985) Lack of binding of bacterial lipopolysaccharide to mouse lung macrophages and restoration of binding by gamma interferon. J Exp Med 162: 1444–1459PubMedGoogle Scholar
  5. Alvaro-Gracia JM, Zvaifler NJ, Firestein GS (1989) Cytokines in chronic inflammatory arthritis. IV. GM-CSF mediated induction of class II MHC antigen on human monocytes: a possible role in rheumatoid arthritis. J Exp Med (170: 865–875 )PubMedGoogle Scholar
  6. Ampel NM, Wing EJ, Waheed A, Shadduck RK (1986) Stimulatory effects of purified macrophage colony-stimulating factor on murine resident peritoneal macrophages. Cell Immunol 97: 344–356PubMedGoogle Scholar
  7. Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB (1987) Expression and secretion of type transforming growth factor by activated human macrophages. Proc Natl Acad Sci USA 84: 6020–6024PubMedGoogle Scholar
  8. Averbook BJ, Yamamoto RS, Ulich TR, Jeffes EW, Masunaka I, Granger GA (1987) Purified native and recombinant human alpha lymphotoxin [tumor necrosis factor ( TNF)-beta] induces inflammatory reactions in normal skin. J Clin Immunol 7: 333–340PubMedGoogle Scholar
  9. Bauer J, Ganter U, Geiger T, Jacobshagen U, Hirano T, Matsuda T, Kishimoto T, Andus T, Acs G, Gerok W, Ciliberto G (1988) Regulation of interleukin-6 expression in cultured human blood monocytes and monocyte-derived macrophages. Blood 72: 1134–1140PubMedGoogle Scholar
  10. Belsoevic M, Davis CE, Meltzer MS, Nacy CA (1988) Regulation of activated macrophage antimicrobial activities. Identification of lymphokines that cooperate with IFN-gamma for induction of resistance to infection. J Immunol 141: 890Google Scholar
  11. Bermudez LE, Young LS (1987) Granulocyte-macrophage colony stimulating factor activates human macrophages to kill Mycobacterium avium complex (Abstr). Clin Res 35:612 AGoogle Scholar
  12. Beutler B, Tkacenko V, Milsark I, Krochin N, Cerami A (1986) Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype. J Exp Med 164: 1791–1796PubMedGoogle Scholar
  13. Bianco C, Eden A, Cohn ZA (1976) The induction of macrophage spreading: role of coagulation factors and the complement system. J Exp Med 144: 1531PubMedGoogle Scholar
  14. Bloom BR, Bennett B (1966) Mechanism of a reaction in vitro associated with delayed type hypersensitivity. Science 153: 80–82PubMedGoogle Scholar
  15. Boraschi D, Censini S, Bartalini M, Tagliabue A (1985) Regulation of arachidonic acid metabolism in macrophages by immune and nonimmune interferons. J Immunol 135: 502–505PubMedGoogle Scholar
  16. Brummer E, Hanson LH, Restrepo A, Stevens DA (1988) In vivo and in vitro activation of pulmonary macrophages by IFN-y for enhanced killing of Paracoccidiodes brasiliensis or Blastomyces dermatitidis. J Immunol 140: 2786–2789PubMedGoogle Scholar
  17. Buchmeier NA, Schreiber RD (1985) Requirement of endogenous interferon-gamma production for resolution of Listeria monocytogenes infection. Proc Natl Acad Sci USA 82: 7404–7408PubMedGoogle Scholar
  18. Carvalho EM, Badaro R, Reed SG, Jones TC, Johnson WD Jr (1985) Absence of gamma interferon and interleukin 2 production during active visceral leishmaniasis. J Clin Invest 76: 2066–2069PubMedGoogle Scholar
  19. Catterall JR, Sharma SD, Remington JS (1986) Oxygen-independent killing by alveolar macrophages. J Exp Med 163: 1113–1131PubMedGoogle Scholar
  20. Celada A, Schreiber RD (1986) Role of protein kinase C and intracellular calcium mobilization in the induction of macrophage tumoricidal activity by interferon gamma. J Immunol 137: 2375–2379Google Scholar
  21. Chen BD-M, Clark CR, Chou T-H (1988 a) Granulocyte/macrophage colony- stimulating factor stimulates monocyte and tissue macrophage proliferation and enhances their responsiveness to macrophage colony-stimulated factor. Blood 71: 997–1002Google Scholar
  22. Chen BD-M, Mueller M, Chou T-H (1988 b) Role of granulocyte/macrophage colony- stimulating factor in the regulation of murine alveolar macrophage proliferation and differentiation. J Immunol 141: 139–144PubMedGoogle Scholar
  23. Chen BD-M, Mueller M, Olencki T (1988 c) Interleukin-3 (IL-3) stimulates the clonal growth of pulmonary alveolar macrophage of the mouse: role of IL-3 in the regulation of macrophage production outside the bone marrow. Blood 72: 685–690Google Scholar
  24. Coleman DL, Chodakewitz J A, Bartiss AH, Mellors JW (1988) Granulocyte- macrophage colony-stimulating factor enhances selective effector functions of tissue-derived macrophages. Blood 72: 573–578PubMedGoogle Scholar
  25. Collart MA, Belin D, Vassalli J-D, de Kossodo S, Vassalli P (1986) y-Interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin-1, and urokinase genes, which are controlled by short lived repressors. J Exp Med 164: 2113–2118Google Scholar
  26. Conkling PR, Greenburg CS, Weinberg JB (1988) Tumor necrosis factor induces tissue factor-like activity in human leukemia cell line U937 and peripheral blood monocytes. Blood 72: 128–133PubMedGoogle Scholar
  27. Crawford RM, Finbloom DS, Ohara J, Paul WE, Meltzer MS (1987) B cell stimulatory factor-1 (interleukin 4) activates macrophages for increased tumoricidal activity and expression of la antigens. J Immunol 139: 135PubMedGoogle Scholar
  28. Currie GA, Basham C (1978) Differential arginine dependence and the selective cytotoxic effects of activated macrophages for malignant cells in vitro. Br J Cancer 38: 653–659PubMedGoogle Scholar
  29. Currie GA, Gyure L, Cifuentes L (1979) Microenvironmental arginine depletion by macrophages in vivo. Br J Cancer 39: 613–620PubMedGoogle Scholar
  30. Czarniecki CW, Chiu HH, Wong GH, McCabe SM, Palladino MA (1988) Transforming growth factor-beta 1 modulates the expression of class II histocompatibility antigens on human cells. J Immunol 140: 4217–4223PubMedGoogle Scholar
  31. David JR (1966) Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci USA 56: 72–77PubMedGoogle Scholar
  32. De Titto E, Catteral JR, Remington JS (1986) Activity of recombinant tumor necrosis factor on Toxoplasma gondii and Trypanosoma cruzi. J Immunol 137: 1342PubMedGoogle Scholar
  33. Ding A, Nathan CF (1987) Trace levels of bacterial lipopolysaccharide prevent interferon-y or tumor necrosis factor-a from enhancing mouse peritoneal macrophage respiratory burst capacity. J Immunol 139: 1971–1977PubMedGoogle Scholar
  34. Ding A, Nathan CF, Stuehr DJ (1988) Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages: comparison of activating cytokines and evidence for independent production. J Immunol 141: 2407–2412PubMedGoogle Scholar
  35. Ding A, Sanchez E, Srimal S, Nathan CF (1989) Macrophages rapidly internalize their tumor necrosis factor receptors in response to bacterial lipopolysaccharide. J Biol Chem 264: 3924–3929PubMedGoogle Scholar
  36. Edwards CK III, Hedegaard HB, Zlotnik A, Gahgadharam PR, Johnston RB Jr, Pabst MJ (1986) Chronic infection due to Mycobacterium intracellular in mice: association with macrophage release of prostaglandin E2 and reversal by injection of in- domethacin, muramyl dipeptide, and interferon-y. J Immunol 136: 1820–1827PubMedGoogle Scholar
  37. Esparza I, Mannel D, Ruppel A, Falk W, Krammer PH (1987) Interferon-y and lymphotoxin or tumor necrosis factor act synergistically to induce macrophage killing of tumor cells and schistosomula of Schistosoma mansoni. J Exp Med 166: 589–594PubMedGoogle Scholar
  38. Espevik T, Figari IS, Shalaby MR, Lackides GA, Lewis GD, Shepard HM, Palladino MA Jr (1987) Inhibition of cytokine production by cyclosporin A and transforming growth factor-ß J Exp Med 166: 571–576Google Scholar
  39. Ezekowitz RAB, Dinauer MC, Jaffe HS, Orkin SH, Newburger PE (1988) Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med 319: 146PubMedGoogle Scholar
  40. Fan XD, Goldberg M, Bloom BR (1988) Interferon-gamma-induced transcriptional activation is mediated by protein kinase C. Proc Natl Acad Sci USA 85: 5122–5125PubMedGoogle Scholar
  41. Fels AOS, Nathan CF, Cohn ZA (1987) H202 release by alveolar macrophages from sarcoid patients and by alveolar macrophages from normals after exposure to recombinant interferons a A, ß, y and 1,25-dihydroxy vitamin D3. J Clin Invest 80: 381–386PubMedGoogle Scholar
  42. Fogelman AM, Seager J, Groopman JE, Berliner JA, Haberland ME, Edwards PA, Golde DW (1983) Lymphokines secreted by an established lymphocyte line modulate receptor-mediated endocytosis in macrophages derived from human monocytes. J Immunol 131: 2368–2373PubMedGoogle Scholar
  43. Forster O, Landy M (eds) (1981) Heterogeneity of mononuclear phagocytes. Academic, LondonGoogle Scholar
  44. Fowles RE, Fajardo IM, Leibowitch JL, David JR (1973) The enhancement of macrophage bacteriostasis by products of activated lymphocytes. J Exp Med 138: 952–964PubMedGoogle Scholar
  45. Gendelman H, Orenstein JM, Martin MA, Ferrua C, Mitra R, Phipps T, Wahl LA, Lane HC, Fauci HS, Burke DS, Skillman D, Meltzer MS (1988) Efficient isolation and propagation of human immunodeficiency virus on recombinant colony- stimulating factor 1-treated monocytes. J Exp Med 167: 1428PubMedGoogle Scholar
  46. Goodman MG, Chenoweth DE, Weigle WO (1982) Induction of interleukin 1 secretion and enhancement of humoral immunity by binding of human C5a to macrophage surface C5a receptors. J Exp Med 156: 912PubMedGoogle Scholar
  47. Grabstein KH, Urdal DL, Tushinski RJ, Mochizuki DY, Price BL, Cantrell MA, Gillis S, Conlon PJ (1986) Induction of macrophage tumoricidal activity by granulocyte- macrophage colony-stimulating factor. Science 232: 506PubMedGoogle Scholar
  48. Granger DL, Hibbs JB Jr, Perfect JR, Durack DT (1988) Specific amino acid ( L- arginine) requirement for the microbiostatic activity of murine macrophages. J Clin Invest 81: 1129Google Scholar
  49. Grau GE, Kindler V, Piguet P-F, Lambert P-H, Vassalli P (1988) Prevention of experimental cerebral malaria by anticytokine antibodies. Interleukin 3 and granulocyte macrophage colony-stimulating factor are intermediates in increased tumor necrosis factor production and macrophage accumulation. J Exp Med 168: 1499–1504PubMedGoogle Scholar
  50. Greil J, Bodendorfer B, Rollinghoff M, Solbach W (1988) Application of recombinant granulocyte-macrophage colony-stimulating factor has a detrimental effect in experimental murine leishmaniasis. Eur J Immunol 18: 1527–1533PubMedGoogle Scholar
  51. Guilbert LJ, Stanley ER (1984) Modulation of receptors for the colony-stimulating factor, CSF-1, by bacterial lipopolysaccharide and CSF-1. J Immunol Methods 73: 17–28PubMedGoogle Scholar
  52. Guyre PM, Morganelli PM, Miller R (1983) Recombinant interferon gamma increases immunoglobulin Fc receptors on cultured human mononuclear phagocytes. J Clin Invest 72: 393–397PubMedGoogle Scholar
  53. Hamilton TA, Bacton DL, Somers SD, Gray PW, Adams DO (1985 a) Interferon- gamma modulates protein kinase C activity in murine peritoneal macrophages. J Biol Chem 260: 1378–1381Google Scholar
  54. Hamilton TA, Rigsbee JE, Scott WA, Adams DO (1985 b) Gamma interferon enhances the secretion of arachidonic acid metabolites from murine peritoneal macrophages stimulated with phorbol diesters. J Immunol 134: 2631–2636Google Scholar
  55. Hampton RY, Golenbock DT, Raetz CRH (1988) Lipid A binding sites in membranes of macrophage tumor cells. J Biol Chem 263:14 802–14 807Google Scholar
  56. Heremans H, Dijkmans R, Sobis H, Vandekerckhove F, Billiau A (1987) Regulation by interferons of the local inflammatory response to bacterial lipopolysaccharide. J Immunol 138: 4175–4179PubMedGoogle Scholar
  57. Herrmann R, Cannistra SA, Levine H, Griffin JD (1985) Expression of interleukin 2 receptors and binding of interleukin 2 by gamma interferon-induced human leukemic and normal monocytic cells. J Exp Med 162: 1111–1116PubMedGoogle Scholar
  58. Hibbs JB Jr, Taintor RR, Vavrin Z (1987 a) Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 235: 473Google Scholar
  59. Hibbs JB Jr, Vavrin Z, Taintor RR (1987 b) L-Arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J Immunol 138: 550–565Google Scholar
  60. Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM (1988) Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157: 87–94PubMedGoogle Scholar
  61. Horiguchi J, Warren MK, Kufe D (1987) Expression of the macrophage-specific colony-stimulating factor in human monocytes treated with granulocyte- macrophage colony-stimulating factor. Blood 69: 1259–1261PubMedGoogle Scholar
  62. Hyslop PA, Hinshaw DB, Halsey WA Jr, Schraufstatter IU, Sauerheber RD, Spragg RG, Jackson JH, Cochrane CH (1988) Mechanisms of oxidant-mediated cell injury. The glycolytic and mitochondrial pathways of ADP phosphorylation are major intracellular targets inactivated by hydrogen peroxide. J Biol Chem 263: 1665–1675PubMedGoogle Scholar
  63. Ichinose Y, Bakouche O, Tsao JY, Fidler IJ (1988) Tumor necrosis factor and IL-1 associated with plasma membranes of activated human monocytes lyse monokine- sensitive but not monokine-resistant tumor cells whereas viable activated monocytes lyse both. J Immunol 141: 512PubMedGoogle Scholar
  64. Inaba K, Steinman RM (1984) Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen presenting cell) requirements for growth and lymphokine release. J Exp Med 160: 1717–1735PubMedGoogle Scholar
  65. Jensen WA, Rose RM, Burke RA Jr, Anton K, Remold HG (1988) Cytokine activation of anti-bacterial activity in human mononuclear phagocytes: comparison of recombinant interferon-y and granulocyte macrophage stimulating factor. Cell Immunol 117: 369–377PubMedGoogle Scholar
  66. Kaufmann SH, Hug E, Vath U, DeLibero G (1987) Specific lysis of Listeria monocytogenes-infected macrophages by class II-restricted L3T4 + T cells. Eur J Immunol 17: 237–246PubMedGoogle Scholar
  67. Kiderlen AF, Kaufmann SHE, Lohmann-Matthes M-L (1984) Protection of mice against the intracellular bacterium Listeria monocytogenes by recombinant immune interferon. Eur J Immunol 14: 964–967PubMedGoogle Scholar
  68. Kindler V, Sappino AP, Grau GE, Piguet PF, Vassalli P (1989) The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 56: 731–740PubMedGoogle Scholar
  69. Klebanoff SJ (1988) Phagocytic cells: products of oxygen metabolism. In: Gallin JI, Goldstein IM, Snyderman R (eds) Inflammation: basic principles and clinical correlates. Raven, New York, pp 391–44Google Scholar
  70. Koeffler HP, Reichel H, Bishop JE, Norman AW (1985) Gamma-interferon stimulates production of 1,25-dihydroxyvitamin D3 by normal human macrophages. Biochem Biophys Res Commun 127: 596–603PubMedGoogle Scholar
  71. Lamperi S, Carozzi S (1988) Interferony (IFN-y) as in vitro enhancing factor of peritoneal macrophage defective bactericidal activity during continuous ambulatory peritoneal dialysis ( CAPD ). Am J Kidney Dis 11: 225–230PubMedGoogle Scholar
  72. Lu L, Walker D, Graham CD, Waheed A, Shadduck RK, Broxmeyer HE (1988) Enhancement of release from MHC class II antigen-positive monocytes of hematopoietic colony stimulating factors CSF-1 and G-CSF by recombinant human tumor necrosis factor-alpha: synergism with recombinant human interferon-gamma. Blood 72: 34–41PubMedGoogle Scholar
  73. Luster AD, Ravetch JV (1987) Biochemical characterization of a y interferon-inducible cytokine. J Exp Med 166: 1084–1097PubMedGoogle Scholar
  74. Mackaness GB (1969) The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med 129: 973–992PubMedGoogle Scholar
  75. Maluish AE, Urba WJ, Longo DL, Overton WR, Coggin D, Crisp ER, Williams R, Sherwin SA, Gordon K, Steis RG (1988) The determination of an immunologically active dose of interferon-gamma in patients with melanoma. J Clin Oncol 6: 434–445PubMedGoogle Scholar
  76. Marietta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS (1988) Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 27: 8706–8711Google Scholar
  77. McCabe RE, Luft BJ, Remington JS (1984) Effect of murine interferon gamma on murine toxoplasmosis. J Infect Dis 150: 961–962PubMedGoogle Scholar
  78. Miller LJ, Bainton DF, Borregaard N, Springer TA (1987) Stimulated mobilization of monocyte Mac-1 and pi50,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. J Clin Invest 80: 535–544PubMedGoogle Scholar
  79. Mokoena T, Gordon S (1985) Human macrophage activation. Modulation of man- nosyl, fucosyl receptor activity in vitro by lymphokines, gamma and alpha interferons, and dexamethasone. J Clin Invest 75: 624–631PubMedGoogle Scholar
  80. Murray HW (1988) Interferon-gamma, the activated macrophage, and host defense against microbial challenge. Ann Intern Med 108: 595–608PubMedGoogle Scholar
  81. Murray HW, Rubin BY, Rothermel CD (1983) Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-y is the stimulating lymphokine. J Clin Invest 72: 1506–1510Google Scholar
  82. Murray HW, Spitalny GL, Nathan CF (1985) Activation of mouse peritoneal macrophages in vitro and in vivo by interferon-gamma. J Immunol 134: 1619–1622PubMedGoogle Scholar
  83. Murray HW, Scavuzzo D, Jacobs JL, (1987 a) In vitro and in vivo activation of human mononuclear phagocytes by gamma interferon: studies with normal and AIDS monocytes. J Immunol 138:2457–2462Google Scholar
  84. Murray HW, Stern J J, Welte K, Rubin BY, Carriero SM, Nathan CF (1987 b) Experimental visceral leishmaniasis: production of interleukin 2 and interferon-y, tissue immune reaction, and response to treatment with interleukin 2 and interferon-y. J Immunol 138: 2290–2297Google Scholar
  85. Mustoe TA, Pierce GF, Thomason A, Gramates P, Sporn MB, Deuel TF (1987) Accelerated healing of incisional wounds in rats induced by transforming growth factorbeta. Science 237: 1333–1336PubMedGoogle Scholar
  86. Nacy CA, Fortier AH, Meitzer MS, Buchmeier NA, Schreiber RD (1985) Macrophage activation to kill Leishmania major, activation of macrophages for intracellular destruction of amastigotes can be induced by both recombinant interferon-gamma and non-interferon lymphokines. J Immunol 135: 3505–3511PubMedGoogle Scholar
  87. Nakagawara A, Nathan CF, Cohn ZA (1981) Hydrogen peroxide metabolism in human monocytes during differentiation in vitro. J Clin Invest 68: 1243–1252PubMedGoogle Scholar
  88. Nathan CF (1982) Secretion of oxygen intermediates: role in effector functions of activated macrophages. Fed Proc 41: 2206–2211PubMedGoogle Scholar
  89. Nathan CF (1983) Macrophage microbicidal mechanisms. Trans R Soc Trop Med Hyg 77: 620–630PubMedGoogle Scholar
  90. Nathan CF (1986) Macrophage activation: some questions. Ann Inst Pasteur 137C: 345–351Google Scholar
  91. Nathan CF (1987 a) Secretory products of macrophages. J Clin Invest 79:319–326Google Scholar
  92. Nathan CF (1987 b) Neutrophil activation on biological surfaces: massive release of hydrogen peroxide in response to products of macrophages and lymphocytes. J Clin Invest 80:1550–1560Google Scholar
  93. Nathan CF (1989) Respiratory burst of adherent human neutrophils: triggering by colony stimulating factors CSF-GM and CSF-G. Blood 73: 301–306PubMedGoogle Scholar
  94. Nathan CF, Cohn ZA (1985) Cellular components of inflammation: monocytes and macrophages. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB (eds) Textbook of rheumatology. Saunders, Philadelphia, pp 144–168Google Scholar
  95. Nathan CF, Terry WD (1977) Decreased phagocytosis by macrophages from BCG- treated mice: induction of the phagocytic defect in normal macrophages given BCG in vitro. Cell Immunol 29: 295–311PubMedGoogle Scholar
  96. Nathan CF, Tsunawaki S (1986) Secretion of toxic oxygen products by macrophages: regulatory cytokines and their effects on the oxidase. Ciba Found Symp 118: 211–230PubMedGoogle Scholar
  97. Nathan CF, Yoshida R (1988) Cytokines: interferon-y. In: Gallin J, Goldstein I, Snyderman R (eds) Inflammation: basic principles and clinical correlates. Raven, New York, pp 229–251Google Scholar
  98. Nathan CF, Remold HG, David JR (1973) Characterization of a lymphocyte factor which alters macrophage functions. J Exp Med 137: 275–290PubMedGoogle Scholar
  99. Nathan CF, Arrick BA, Murray HW, DeSantis NM, Cohn ZA (1981) Tumor cell antioxidant defenses: inhibition of the glutathione redox cycle enhances macrophage-mediated cytolysis. J Exp Med 153: 766–782PubMedGoogle Scholar
  100. Nathan CF, Murray HW, Weibe ME, Rubin BY (1983) Identification of interferon-y as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158: 670–689PubMedGoogle Scholar
  101. Nathan CF, Prendergast TJ, Weiber JE, Stanley ER, Platzer E, Remold HG, Welte K, Rubin BY, Murray HW (1984) Activation of human macrophages: comparison of other cytokines with interferon-y. J Exp Med 160: 600–605PubMedGoogle Scholar
  102. Nathan CF, Horowitz CR, de la Harpe J, Vadhan-Raj S, Sherwin SA, Oettgen HF, Krown SE (1985) Administration of recombinant interferon-y to cancer patients enhances monocyte secretion of hydrogen peroxide. Proc Natl Acad Sei USA 82: 8686–8690Google Scholar
  103. Nathan CF, Kaplan G, Levis WR, Nusrat A, Witmer MD, Sherwin SA, Job CK, Horowitz CR, Steinman RM, Cohn ZA (1986) Local and systemic effects of low doses of recombinant interferon-y after intradermal injection in patients with lepromatous leprosy. N Engl J Med 315: 6–14PubMedGoogle Scholar
  104. Nathan C, Campanelli D, Ding A, de la Harpe J, Gabay J, Srimal S, Stuehr D, Tsunawaki S, Yoshida R (1988) Regulatory and effector molecules for cytotoxicity by phagocytes. In: Schwarz M (ed) Proceedings of the Centennary of the Institut Pasteur. Elsevier, Amsterdam, pp 267–282Google Scholar
  105. O’Donnell-Tormey J, Nathan CF, Lanks K, Deboer C, de la Harpe J (1987) Secretion of pyruvate: an antioxidant defense of mammalian cells. J Exp Med 165: 500–514Google Scholar
  106. Onozaki K, Matsushima K, Aggarwal BB, Oppenheim JJ (1985) Human interleukin 1 is a cytocidal factor for several tumor cell lines. J Immunol 135: 3962PubMedGoogle Scholar
  107. Perussia B, Dayton ET, Lazarus R, Fanning V, Trinchieri G (1983) Immune interferon induces the receptor for monomeric IgGx on human monocytic and myeloid cells. J Exp Med 158: 1092PubMedGoogle Scholar
  108. Philip R, Epstein LB (1986) Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, y-interferon and interleukin-1. Nature 323: 86–89PubMedGoogle Scholar
  109. Radzioch D, Varesio L (1988) Protein kinase C inhibitors block the activation of macrophages by IFN-ß but not by IFN-y. J Immunol 140: 1259–1263PubMedGoogle Scholar
  110. Ralph P, Nakoinz I (1987) Stimulation of macrophage tumoricidal activity by the growth and differentiation factor CSF-1. Cell Immunol 105: 270–279PubMedGoogle Scholar
  111. Ralph P, Nakoinz I, Rennick D (1988) Role of interleukin 2, interleukin 4, and a, ß, and y interferon in stimulating macrophage antibody-dependent tumoricidal activity. J Exp Med 167: 712–717PubMedGoogle Scholar
  112. Rappolee DA, Mark D, Banda MJ, Werb Z (1988) Wound macrophages express transforming growth factor-a and other growth factors in vivo: analysis by mRNA phenotyping. Science 241: 708–712PubMedGoogle Scholar
  113. Reed SG (1988) In vivo administration of recombinant IFN-y induces macrophage activation, and prevents acute disease, immune suppression, and death in experimental Trypanosoma cruzi infections. J Immunol 140: 4342–4347PubMedGoogle Scholar
  114. Reed SG, Nathan CF, Pihl DL, Rodricks P, Shanebeck K, Conlon PJ, Grabstein KH (1987) Recombinant granulocyte-macrophage colony stimulating factor activates macrophages to inhibit Trypanosoma cruzi and release hydrogen peroxide: comparison to interferon-y. J Exp Med 166: 1734–1746PubMedGoogle Scholar
  115. Reiner NE, Ng W, Ma T, McMaster WR (1988) Kinetics of y interferon binding and induction of histocompatibility complex class II mRNA in Leishmania-infected macrophages. Proc Natl Acad Sei USA 85: 4330–4334Google Scholar
  116. Robinson BW, McLemore TL, Crystal RG (1985) Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis. J Clin Invest 75: 1488–1495PubMedGoogle Scholar
  117. Rosen H, Gordon S (1987) Monoclonal antibody to the murine type 3 complement receptor inhibits adhesion of myelomonocytic cells in vitro and inflammatory cell recruitment in vivo. J Exp Med 166: 1685–1701PubMedGoogle Scholar
  118. Rothermel CD, Rubin BY, Murray HW (1983) y-Interferon is the factor in lymphokine that activates human macrophages to inhibit intracellular Chlamydia psittaci replication. J Immunol 131: 2542–2544Google Scholar
  119. Rothstein JL, Schreiber H (1988) Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice. Proc Natl Acad Sci USA 85: 607–611PubMedGoogle Scholar
  120. Rothstein JL, Flint TF, Schreiber H (1988) Tumor necrosis factor/cachectin. Induction of hemorrhagic necrosis in normal tissue requires the fifth component of complement ( C5 ). J Exp Med 168: 2007–2021Google Scholar
  121. Samuel NM, Grange JM, Samuel S, Lucas S, Owilli OM, Adaila S, Leigh IM, Navarrette C (1987) A study of the effects of intradermal administration of recombinant gamma interferon in lepromatous leprosy patients. Lepr Rev 58: 389–400PubMedGoogle Scholar
  122. Schlesinger L, Musson RA, Johnston RB Jr (1984) Functional and biochemical studies of multinucleated giant cells derived from the culture of human monocytes. J Exp Med 159: 1289–1294PubMedGoogle Scholar
  123. Schraufstatter I, Hyslop PA, Jackson JH, Cochrane CG (1988) Oxidant-induced DNA damage of target cells. J Clin Invest 82: 1040–1050PubMedGoogle Scholar
  124. Schreiber RD, Pace JL, Russell SW, Altman A, Katz DH (1983) Macrophage- activating factor produced by a T cell hybridoma: physicochemical and biosynthetic resemblance to y-interferon. J Immunol 131: 826PubMedGoogle Scholar
  125. Schreiber RD, Hicks LJ, Celada A, Buchmeier NA, Gray PW (1985) Monoclonal antibodies to murine y-interferon which differentially modulate macrophage activation and antiviral activity. J Immunol 134: 1609–1618PubMedGoogle Scholar
  126. Sechler JMG, Malech HL, White CJ, Gallin JI (1988) Recombinant human interferon- y reconstitutes defective phagocyte function in patients with chronic granulomatous disease of childhood. Proc Natl Acad Sci USA 85: 4874–4878PubMedGoogle Scholar
  127. Sibley LD, Hunter SW, Brennan PJ, Krahenbuhl JL (1988) Mycobacterial lipoarabinomannan inhibits gamma interferon-mediated activation of macrophages. Infect Immun 56: 1232–1236PubMedGoogle Scholar
  128. Sisson SD, Dinarello CD (1988) Production of interleukin-la, interleukin-1ß and tumor necrosis factor by human mononuclear cells stimulated with granulocyte- macrophage colony-stimulating factor. Blood 72: 1368–1374PubMedGoogle Scholar
  129. Steeg PS, Moore RN, Johnson M, Oppenheim JJ (1982) Regulation of murine macro¬phage la antigen expression by a lymphokine with immune interferon activity. J Exp Med 156: 1780–1793PubMedGoogle Scholar
  130. Stewart CC (1980) Formation of colonies by mononuclear phagocytes outside the bone marrow. In Mononuclear Phagocytes: Functional Aspects. R. van Furth, ed. Martinus Nijhoff, Boston 377–416Google Scholar
  131. Stewart CC, Lin H, Adles C (1975) Proliferation and colony-forming ability of peritoneal exudate cells in liquid culture. J Exp Med 141: 1114–1132PubMedGoogle Scholar
  132. Strassman G, Springer TA, Adams DO (1985) Studies on antigens associated with the activation of murine mononuclear phagocytes: kinetics of and requirements for induction of lymphocyte function-associated (LFA-1) antigen in vitro. J Immunol 135: 147–151Google Scholar
  133. Strassman G, Springer TA, Somers SD, Adams DO (1986) Mechanisms of tumor cell capture by activated macrophages: evidence for involvement of lymphocyte function-associated ( LFA)-l antigen. J Immunol 136: 4328–4333Google Scholar
  134. Strunk RC, Cole FS, Perlmutter DH, Colten HR (1985) y-Interferon increases expression of class III complement genes C2 and factor B in human monocytes and in murine fibroblasts transfected with human C2 and factor B genes. J Biol Chem 260: 15280–15285PubMedGoogle Scholar
  135. Stuehr DJ, Marietta MA (1987) Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-y. J Immunol 139: 518PubMedGoogle Scholar
  136. Stuehr DJ, Nathan CF (1989) Nitric oxide: a macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 169: 1543–1555PubMedGoogle Scholar
  137. Stuehr DJ, Gross SS, Sakuma I, Levi R, Nathan CF (1989 a) Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide. J Exp Med 169: 1011–1020PubMedGoogle Scholar
  138. Stuehr DJ, Kwon NS, Gross SS, Thiel BA, Levi R, Nathan CF (1989 b) Synthesis of nitrogen oxides from L-arginine by macrophage cytosol: requirement for inducible and constitutive components. Biochem Biophys Res Commun 161: 420–426PubMedGoogle Scholar
  139. Sugarman BJ, Aggarwal BB, Hass PE, Figari IS, Palladino MA Jr, Shepard HM (1985) Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vivo. Science 230: 943–945PubMedGoogle Scholar
  140. Suzuki Y, Orellana MA, Schreiber RD, Remington JS (1988) Interferon-y: the major mediator of resistance against Toxoplasma gondii. Science 240: 516–518PubMedGoogle Scholar
  141. Swaim MW, Pizzo SV (1988) Methionine sulfoxide and the oxidative regulation of plasma proteinase inhibitors. J Leuk Biol 43: 365–380Google Scholar
  142. Szuro-Sudol A, Nathan CF (1982) Suppression of macrophage oxidative metabolism byproducts of malignant and nonmalignant cells. J Exp Med 156: 945–961PubMedGoogle Scholar
  143. Szuro-Sudol A, Murray HW, Nathan CF (1983) Suppression of macrophage microbicidal activity by a tumor cell product. J Immunol 131: 384–387PubMedGoogle Scholar
  144. Thorens B, Mermod J-J, Vassalli P (1987) Phagocytosis and inflammatory stimuli induce GM-CSF mRNA in macrophages through posttranscriptional regulation. Cell 48: 671–679PubMedGoogle Scholar
  145. Thurman GB, Braude I A, Gray PW, Oldham RK, Stevenson HC (1985) MIF-like activity of natural and recombinant human interferon-gamma and their neutralization by monoclonal antibody. J Immunol 134: 305–309PubMedGoogle Scholar
  146. Tovey MG, Streuli M, Gresser I, Gugenheim J, Blanchard B, Guymarho J, Vignaux F, Gigou M (1987) Interferon messenger RNA is produced constitutively in the organs of normal individuals. Proc Natl Acad Sci USA 84: 5038PubMedGoogle Scholar
  147. Trinchieri G, Santoli D (1978) Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis. J Exp Med 147: 1314–1334PubMedGoogle Scholar
  148. Tsunawaki S, Nathan CF (1986) Macrophage deactivation: altered kinetic properties of the superoxide-producing enzyme after exposure to tumor cell-conditioned medium. J Exp Med 164: 1319–1331PubMedGoogle Scholar
  149. Tsunawaki S, Sporn M, Ding A, Nathan CF (1988) Macrophage deactivation by transforming growth factor-ß. Nature 334: 260–262PubMedGoogle Scholar
  150. Tsunawaki S, Sporn M, Nathan CF (1989) Comparison of transforming growth factor p and a macrophage-deactivating polypeptide from tumor cells. J Immunol 142: 3462–3468PubMedGoogle Scholar
  151. Tushinski RJ, Oliver IT, Guilbert LJ, Tynan PW, Warner JR, Stanley ER (1982) Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell 28: 71–81PubMedGoogle Scholar
  152. Unanue ER, Allen PM (1987) The basis for the immunoregulatory role of macrophages and other accessory cells. Science 236: 551–557PubMedGoogle Scholar
  153. Varesio L, Blasi E, Thurman GB, Talmadge JE, Wiltrout RH, Herberman RB (1984) Potent activation of mouse macrophages by recombinant interferon-gamma. Cancer Res 44: 4465–1469PubMedGoogle Scholar
  154. Vellenga E, Rambaldi A, Ernst TJ, Ostapovicz D, Griffin JD (1988) Independent regulation of M-CSF and G-CSF gene expression in human monocytes. Blood 71: 1529–1532PubMedGoogle Scholar
  155. Vlassara H, Valinsky J, Brownlee M, Cerami C, Nishimoto S, Cerami A (1987) Advanced glycosylation endproducts on erythrocyte cell surface induce receptor- mediated phagocytosis by macrophages: a model for turnover of aging cells. J Exp Med 166: 539–549PubMedGoogle Scholar
  156. Wahl SM, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB, Sporn MB (1987) Transforming growth factor type ßinduces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 84: 5788–5792PubMedGoogle Scholar
  157. Walker EB, Maino V, Sanchez-Lanier M, Warner N, Stewart C (1984) Murine gamma interferon activates the release of a macrophage-derived la-inducing factor that transfers la inductive capacity. J Exp Med 159: 1532–1547PubMedGoogle Scholar
  158. Wang JM, Collela S, Allavena P, Mantovani A (1987) Chemotactic activity of human recombinant granulocyte-macrophage colony-stimulating factor. Immunology 60: 439–444PubMedGoogle Scholar
  159. Wang JM, Griffin JD, Rambaldi A, Chen ZG, Mantovani A (1988) Induction of monocyte migration by recombinant macrophage colony-stimulating factor. J Immunol 141: 575–579PubMedGoogle Scholar
  160. Ward PA, Remold HG, David JR (1969) Leukotactic factor produced by sensitized leukocytes. Science 163: 1079–1082PubMedGoogle Scholar
  161. Weinberg JB, Hobbs MM, Misukonis MA (1985) Phenotypic characterization of gamma interferon-induced human monocyte polykaryons. Blood 66: 1241–1246PubMedGoogle Scholar
  162. Weinshank RL, Luster AD, Ravetch JV (1988) Function and regulation of a murine macrophage-specific IgG Fc receptor. J Exp Med 167: 1909PubMedGoogle Scholar
  163. Weiser WY, van Niel A, Clark SC, David JR, Remold HG (1987) Recombinant human granulocyte/macrophage colony-stimulating factor activates intracellular killing of Leishmania donovani by human monocyte-derived macrophages. J Exp Med 166: 1436–1446PubMedGoogle Scholar
  164. Wilson CB, Westall J (1985) Activation of neonatal and adult human macrophages by alpha, beta, and gamma interferons. Infect Immun 49: 351–356PubMedGoogle Scholar
  165. Wright SD, Detmers PA, Jong MT, Meyer BC (1986) Interferon-gamma depresses binding of ligand by Cdb and C3bi receptors on cultured human monocytes, an effect reversed by flbronectin. J Exp Med 163: 1245–1259PubMedGoogle Scholar
  166. Yoshida R, Murray HW, Nathan CF (1988) Two classes of interferon-y receptors on human macrophages: blockade of the high-affinity sites by interferon-a or -ß. J Exp Med 167: 1171–1185PubMedGoogle Scholar
  167. Zoeller RA, Morand OH, Raetz CR (1988) A possible role for plasmalogens in protecting animal cells against photosensitized killing. J Biol Chem 263: 11 590–11596Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • C. F. Nathan

There are no affiliations available

Personalised recommendations