, Volume 2, Issue 3, pp 239–256 | Cite as

Mast cell-mediated reactions of host defense and tissue injury

The regulatory role of eosinophil polymorphonuclear leukocytes
  • Edward J. Goetzl


Immunological stimulation of mast cells, by way of either IgE- or IgG-directed reactions, initiates the rapid release of an array of chemical mediators. The predominant local tissue effects of these mediators collectively constitute a defensive response of the host. The early humoral phase of defense is exemplified by the alterations in microvascular permeability induced by histamine which provide a local concentration of immunoglobulins and complement components. The later cellular phase of defense is composed of the PMN leukocytes that accumulate in response to mast cell-derived chemotactic principles and which phagocytose and degrade opsonized foreign material, thus eliminating the inciting stimulus. Of the several endogenous regulatory mechanisms which act to contain the immediate hypersensitivity reaction, the eosinophil has a special role since it is specifically attracted to sites of mast cell activation and has selective concentrations of several enzymes which degrade the mast cell-derived chemical mediators. Failure of the local regulatory processes can permit the mast cell responses of host defense to become pathological reactions leading to tissue injury by virtue of persistence of high levels of humoral mediators and/or increasing infiltration with PMN leukocytes.


Mast Cell Histamine Host Defense Mast Cell Activation Defensive Response 
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. 1.
    Riley, J.F. 1959. The Mast Cells. Livingstone, Edinburgh.Google Scholar
  2. 2.
    Brinkman, G.L. 1968. The mast cell in normal human bronchus and lung.J. Ultrastruct. Res. 23:115.Google Scholar
  3. 3.
    Patterson, R., andI.M. Suszko. 1971. Primate respiratory mast cells. Reactions with ascaris antigen and anti-heavy chain sera.J. Immunol. 196:1274.Google Scholar
  4. 4.
    Feltkamp-Vroon, T.M., P.J. Stallman, R.C. Analberse, andE.E. Reerink-Bronkers. 1975. Immunofluorescence studies on renal tissue, tonsils, adenoids, nasal polyps and skin of atopic and non-atopic patients with special reference to IgE.Clin. Immunol. Immunopathol. 4:392.Google Scholar
  5. 5.
    Tada, T., andK. Ishizaka, 1970. Distribution of IgE-forming cells in lymphoid tissues of the human and monkey.J. Immunol. 104:377.Google Scholar
  6. 6.
    Ishizaka, T., K. Ishizaka, andH. Tomioka. 1972. Release of histamine and slowreacting substance of anaphylaxis (SRS-A) by IgE-anti-IgE reactions on monkey mast cells.J. Immunol. 108:513.Google Scholar
  7. 7.
    Austen, K.F., S.I. Wasserman, andE.J. Goetzl. 1976. Mast cell-derived mediators: Structural and functional diversity and regulation of expression.In Molecular and Biological Aspects of the Acute Allergic Reaction. S.G.O. Johansson, K. Strandberg, and B. Uvnäs, editors. Plenum Press, New York. 293.Google Scholar
  8. 8.
    Benveniste, J. 1974. Platelet activating factor, a new mediator of anaphylaxis and immune complex deposition from human and rabbit basophils.Nature 249:581.Google Scholar
  9. 9.
    Bogart, D.B., andD.J. Stechschulte. 1974. Release of platelet activating factor from human lung.Clin. Res. 22:652A (abstract).Google Scholar
  10. 10.
    Sherman, W.B., andP.M. Seebohm. 1950. Passive transfer of cold urticaria.J. Allergy 21:414.Google Scholar
  11. 11.
    Houser, D.D., C.E. Arbesman, K. Ito, andK. Witcher. 1970. Cold urticaria: Immunologie studies.Am. J. Med. 49:23.Google Scholar
  12. 12.
    Rose, B.. 1954. Histamine, hormones, and hypersensitivity.J. Allergy 25:168.Google Scholar
  13. 13.
    Kaplan, A.P., L. Gray, R.E. Shaff, Z. Horakova, andM.A. Beaven. 1975. In vivo studies of mediator release in cold urticaria and cholingeric urticaria.J. Allergy Clin. Immunol. 55:394.Google Scholar
  14. 14.
    Soter, N.A., S.I. Wasserman, andK.F. Austen. 1976. Cold urticaria: Release into the circulation of histamine and eosinophil chemotactic factor of anaphylaxis during cold challenge.N. Engl. J. Med. 294:687.Google Scholar
  15. 15.
    McCarthy, D.S., andJ. Pepys. 1971. Allergic bronchopulmonary aspergillosis. Clinical immunology: (2) Skin, nasal and bronchial tests.Clin. Allergy 1:415.Google Scholar
  16. 16.
    Dolovich, J., F.E. Hargreave, R. Chalmers, K.J. Shier, J. Gauldie, andJ. Bienenstock. 1972. Late cutaneous allergic responses in isolated IgE-dependent reactions.J. Allergy Clin. Immunol. 49:43.Google Scholar
  17. 17.
    Goetzl, E.J., S.I. Wasserman, andK.F. Austen. 1975. Eosinophil polymorphonuclear leukocyte function in immediate hypersensitivity.Arch. Pathol. 99:1.Google Scholar
  18. 18.
    Goetzl, E.J., and K.F.Austen. 1977. The generation, function and disposition of chemical mediators of the mast cell in immediate hypersensitivity.In Textbook of Immunopharmacology (in press).Google Scholar
  19. 19.
    Ishizaka, T. 1976. Functions and development of cell receptors for IgE.In Molecular and Biological Aspects of the Acute Allergic Reaction. S.G.O. Johansson, K. Strandberg, and B. Uvnäs, editors. Plenum Press, New York. 199.Google Scholar
  20. 20.
    Parish, W.E. 1974. Skin sensitizing non-IgE antibodies: Association between human IgG S-TS and IgG4.In Progress in Immunology II, Vol. 4. L. Brent and J. Holborow, editors. North-Holland Publishing, Amsterdam. 19.Google Scholar
  21. 21.
    Dvorak, A.M., M.C. Mihm, Jr., andH.F. Dvorak. 1976. Degranulation of basophilic leukocytes in allergic contact dermatitis in man.J. Immunol. 116:687.Google Scholar
  22. 22.
    Dvorak, H.F., A.M. Dvorak, andW.H. Churchill. 1973. Immunologie rejection of diethylnitrosoamine-induced hepatomas in strain-2 guinea pigs. Participation of basophilic leukocytes and macrophage aggregates.J. Exp. Med. 137:751.Google Scholar
  23. 23.
    Kaliner, M., andK.F. Austen. 1973. A sequence of biochemical events in the antigeninduced release of chemical mediators from sensitized human lung tissue.J. Exp. Med. 138:1077.Google Scholar
  24. 24.
    Lawson, D., M.C. Raff, B. Gomperts, C. Fewtrell, andB. Gilula. 1976. Molecular events in membrane fusion occurring during mast cell degranulation.In Molecular and Biological Aspects of the Acute Allergic Reaction. S.G.O. Johansson, K. Strandberg, and B. Uvnäs, editors. Plenum Press, New York. 272.Google Scholar
  25. 25.
    Uvnäs, B.. 1974. Histamine storage and release.Fed. Proc. 33:2172.Google Scholar
  26. 26.
    Lewis, R.A., S.I. Wasserman, E.J. Goetzl, andK.F. Austen. 1974. Formation of SRS-A in human lung tissue and cells before release.J. Exp. Med. 140:1133.Google Scholar
  27. 27.
    Lichtenstein, L.M., andS. Margolis. 1968. Histamine release in vitro: Inhibition by catecholamines and methylxanthines.Science 161:902.Google Scholar
  28. 28.
    Orange, R.P., M.A. Kaliner, andK.F. Austen. 1971. The immunological release of histamine and slow reacting substance of anaphylaxis from human lung. II. Influence of cellular levels of cyclic AMP.Fed. Proc. 30:1725.Google Scholar
  29. 29.
    Lichtenstein, L.M., andE. Gillespie. 1973. Inhibition of histamine release by histamine is controlled by an H2 receptor.Nature (London) 244:287.Google Scholar
  30. 30.
    Kaliner, M., R.P. Orange, andK.F. Austen. 1972. Immunological release of histamine and slow reacting substance of anaphylaxis from human lung. IV. Enhancement by cholinergic and alpha-adrenergic stimulation.J. Exp. Med. 136:556.Google Scholar
  31. 31.
    Kaliner, M., andK.F. Austen. 1974. Hormonal control of the immunologic release of histamine and slow reacting substance of anaphylaxis from human lung.In Cylic AMP, Cell Growth, and the Immune Response. E. Braun, L. M. Lichtenstein, and C.W. Parker, editors. Springer-Verlag, New York. 163.Google Scholar
  32. 32.
    Orange, R.P.. 1974. The formation and release of slow-reacting substance of anaphylaxis in human lung tissues,In Progress in Immunology II. Vol. 4. L. Brent and J. Holborow, editors. North-Holland Publishing, Amsterdam. 29.Google Scholar
  33. 33.
    Sullivan, T.J., L.R. Seyfried, andC.W. Parker. 1975. Histamine synthesis in rat mast cells.Clin. Res. 23:298A.Google Scholar
  34. 34.
    Drazen, J.M., andK.F. Austen. 1974. Effects of intravenous administration of slow reacting substance of anaphylaxis, histamine, bradykinin and prostaglandin F on pulmonary mechanics in the guinea pig.J. Clin. Invest. 53:1679.Google Scholar
  35. 35.
    Black, J.W., W.A.M. Duncan, C.J. Durant, C.R. Ganellin, andE.M. Parsons. 1972. Definition and antagonism of histamine H2-receptors.Nature (London) 236:385.Google Scholar
  36. 36.
    Gold, W.M.. 1973. Cholinergic pharmacology in asthma.In Asthma: Physiology, Immunopharmacology, and Treatment. K.F. Austen and L.M. Lichtenstein, editors. Academic Press, New York. 169.Google Scholar
  37. 37.
    Nadel, J.A.. 1973. Neurophysiologic aspects of asthma.In Asthma: Physiology, Immunopharmacology, and Treatment. K.F. Austen and L.M. Lichtenstein, editors. Academic Press, New York. 29.Google Scholar
  38. 38.
    Rocklin, R.E.. 1976. Modulation of cellular immune responses in vivo and in vivo by histamine-receptor-bearing lymphocytes.J. Clin. Invest. 57:1051.Google Scholar
  39. 39.
    Clark, R.A.F., J.I. Gallin, andA.P. Kaplan. 1975. The selective eosinophil chemotactic activity of histamine.J. Exp. Med. 142:1462.Google Scholar
  40. 40.
    Clark, R.A.F., J.A. Sandler, J.I. Gallin, andA.P. Kaplan. 1977. Histamine modulation of eosinophil migration.J. Immunol. 118:137.Google Scholar
  41. 41.
    Beaven, M.A., S. Jacobsen, andZ. Horakova. 1972. Modification of the enzymatic isotopic assay of histamine and its application to measurement of histamine in tissues, serum and urine.Clin. Chim. Acta 37:91.Google Scholar
  42. 42.
    Kay, A.B., D.J. Stecyschulte, andK.F. Austen. 1971 An eosinophil leukocyte chemotactic factor of anaphylaxis.J. Exp. Med. 133:602.Google Scholar
  43. 43.
    Kay, A.B., andK.F. Austen. 1971. The IgE-mediated release of an eosinophil leukocyte chemotactic factor from human lung.J. Immunol. 107:899.Google Scholar
  44. 44.
    Goetzl, E.J., andK.F. Austen. 1976. Specificity and modulation of the eosinophil polymorphonuclear leukocyte response to the eosinophil chemotactic factor of anaphylaxis (ECF-A).In Molecular and Biological Aspects of the Acute Allergic Reaction. S.G.O. Johansson, K. Strandberg, and B. Uvnäs, editors. Plenum Press, New York. 417.Google Scholar
  45. 45.
    Goetzl, E.J., andK.F. Austen. 1975. Purification and synthesis of eosinophilotactic tetrapeptides of human lung tissue: Identification as eosinophil chemotactic factor of anaphylaxis.Proc. Natl. Acad. Sci. U.S.A. 72:4123.Google Scholar
  46. 46.
    Goetzl, E.J.. 1976. Modulation of human eosinophil polymorphonuclear leukocyte migration and function.Am. J. Pathol. 85:419.Google Scholar
  47. 47.
    Turnbull, L.W., D.P. Evans, andA.B. Kay. 1977. Human eosinophils, acidic tetrapeptides (ECF-A) and histamine. Interactions in vitro and in vivo.Immunology 32:57.Google Scholar
  48. 48.
    Goetzl, E.J., andK.F. Austen. 1976. Structural determinants of the eosinophil chemotactic activity of the acidic tetrapeptides of eosinophil chemotactic factor of anaphylaxis.J. Exp. Med. 144:1324.Google Scholar
  49. 49.
    R.N. Boswell, K.F. Austen, andE.J. Goetzl. 1977. Immunologic release of eosinophil chemotactic factors (ECF) from purified rat peritoneal mast cells (RPMC)Fed. Proc. 36:1328A.Google Scholar
  50. 50.
    Lewis, R.A., E.J. Goetzl, S.I. Wasserman, F.H. Valone, R.H. Rubin, andK.F. Austen. 1975. The release of four mediators of immediate hypersensitivity from human leukemic basophils.J. Immunol. 114:87.Google Scholar
  51. 51.
    Yurt, R.W., R.W. Leid, jr., K.F. Austen, andJ.E. Silbert. 1977. Native heparin from rat peritoneal mast cells.J. Biol. Chem. 252:518.Google Scholar
  52. 52.
    Yurt, R.W., R.W. Leid, jr., J. Spragg, andK.F. Austen. 1977. Immunologic release of heparin from purified rat peritoneal mast cells.J. Immunol. 118:1201.Google Scholar
  53. 53.
    Lagunoff, D., andE.P. Benditt. 1963. Proteolytic enzymes of mast cells.Ann. N. Y. Acad. Sci. 103:185.Google Scholar
  54. 54.
    Lagunoff, S. 1968. The properties of mast cell proteases.Biochern. Pharm. (Suppl.) 17:221.Google Scholar
  55. 55.
    Orange, R.P., R.C. Murphy, M.L. Karnovsky, andK.F. Austen. 1973. The physicochemical characteristics and purification of slow reacting substance of anaphylaxis.J. Immunol. 110:760.Google Scholar
  56. 56.
    Orange, R.P., R.C. Murphy, andK.F. Austen. 1974. Inactivation of slow reacting substance of anaphylaxis (SRS-A) by arylsulfatases.J. Immunol. 113:316.Google Scholar
  57. 57.
    Wasserman, S.I., E.J. Goetzl, andK.F. Austen. 1975. Inactivation of slow reacting substance of anaphylaxis by human eosinophil arylsulfatase.J. Immunol. 114:645.Google Scholar
  58. 58.
    Wasserman, S.I., andK.F. Austen. 1976. Arylsulfatase B of human lung: Isolation, characterization and interaction with slow reacting substance of anaphylaxis.J. Clin. Invest. 57:738.Google Scholar
  59. 59.
    Benveniste, J., P.H. Henson, andC.G. Cochrane. 1972. Leukocyte-dependent histamine release from rabbit platelets.J. Exp. Med. 136:1365.Google Scholar
  60. 60.
    Kater, L. A., E.J. Goetzl, andK.F. Austen. 1976. Isolation of human eosinophil phospholipase D.J. Clin. Invest. 57:1173.Google Scholar
  61. 61.
    Samuelsson, B., M. Hamberg, C. Malmsten, andJ. Svensson. 1976. The role of prostaglandin endoperoxides and thromboxanes in platelet aggregation.In Advances in Prostaglandin and Thromboxane Research, Vol. 2. B. Samuelsson and R. Paoletti, editors. Raven Press, New York. 737.Google Scholar
  62. 62.
    Smith, A.P., andM.F. Cuthbert. 1976. The response of normal and asthmatic subjects to prostaglandins E2 and F by different routes and their significance in asthma.In Advances in Prostaglandin and Thromboxane Research, Vol. 1. B. Samuelsson and R. Paoletti, editors. Raven Press, New York. 449.Google Scholar
  63. 63.
    Goetzl, E.J., J.M. Woods, andR.R. Gorman. 1977. Stimulation of human eosinophil and neutrophil polymorphonuclear leukocyte chemotaxis and random migration by 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid.J. Clin. Invest. 59:197.Google Scholar
  64. 64.
    Tauber, A.I., M.A. Kaliner, D.J. Stechschulte, andK.F. Austen. 1973. Prostaglandins and the immunological release of chemical mediators from human lung.In Prostaglandins and Cyclic AMP: Biological Action and Clinical Application. R. Kahn, editor. Academic Press, New York. 29.Google Scholar
  65. 65.
    Czarnetski, B.M., W. König, andL.M. Lichtenstein. 1976. Antigen-induced eosinophil chemotactic factor (ECF) release by human leukocytes.Inflammation 1:201.Google Scholar
  66. 66.
    Czarnetski, B., W. König, andL.M. Lichtenstein. 1976. Eosinophil chemotactic factor (ECF). 1. Release from polymorphonuclear leukocytes by the calcium ionophore A23187.J. Immunol. 117:119.Google Scholar
  67. 67.
    Goetzl, E.J., R.H. Rubin, J. McDonough, A.H. Tashjian, Jr., andK.F. Austen. 1976. Production of eosinophilotactic peptides by bronchogenic carcinoma in situ and in vitro.Clin. Res. 24:447A.Google Scholar
  68. 68.
    Orr, T.S.C., M.C. Pollard, J. Gwilliam. 1970. Mode of action of disodium cromoglycate, studies on immediate type hypersensitivity reactions using “double sensitization” with two antigenically distinct rat reagins.Clin. Exp. Immunol. 7:745.Google Scholar
  69. 69.
    Siraganian, R.P., andW.A. Hook. 1976. Complement-induced histamine release from human basophils. II. Mechanisms of the histamine release reaction.J. Immunol. 116:639.Google Scholar
  70. 70.
    Grant, J.A., L. Settle, E.B. Whorton, andE. Dupree. 1976. Complement-mediated release of histamine from human basophils. II. Biochemical characterization of the reaction.J. Immunol. 117:450.Google Scholar
  71. 71.
    Augstein, J., J.B. Farmer, T.B. Lee, P. Sheard, andM.L. Tattersall. 1973. Selective inhibitor of slow-reacting substance of anaphylaxis.Nature (London) New Biol. 245:215.Google Scholar
  72. 72.
    Zeiger, R.S., D.L. Yurdin, andH.R. Colten. 1976. Histamine metabolism. II. Cellular and subcellular localization of the catabolic enzymes, histaminase, and histamine methyl transferase in human leukocytes.J. Allergy Clin. Immunol. 58:172.Google Scholar

Copyright information

© Plenum Publishing Corporation 1977

Authors and Affiliations

  • Edward J. Goetzl
    • 1
    • 2
  1. 1.Department of MedicineHarvard Medical SchoolBoston
  2. 2.Department of MedicineThe Robert B. Brigham HospitalBoston

Personalised recommendations