Advertisement

Mediators of Asthma Derived from Arachidonic Acid

  • R. A. Lewis
  • J.-L. Robin

Abstract

The cell types which are normally resident in the human lung and the variety of inflammatory leukocytes that can infiltrate pulmonary tissue in the course of inflammatory lung diseases each have phospholipids as major plasma membrane components. When a cell is perturbated by a stimulus that alters the relative quantities and spacial distributions of phospholipids, phospholipase A2 [1] and/or phospholipase C in concert with diglyceride lipase [2, 3] are also activated, resulting in the release of arachidonic acid for oxidative metabolism to prostaglandins (PGs), thromboxane (Tx), monohydroxy derivatives of arachidonic acid (HETEs), and/or leukotrienes (LTs). The spectrum of oxidative products is dictated by the specificities of the enzymes present in the cellular microenvironment; arachidonic acid may be metabolized to products in the cell from which it is released or by other cells in the immediate vicinity. Additionally, the effects of specific oxidative metabolites of arachidonic acid on target cells may include modification of the capacities of those cells to generate and release additional mediators of inflammation.

Keywords

Arachidonic Acid Systemic Mastocytosis Arachidonic Acid Metabolite Arachidonic Acid Release Inflammatory Lung Disease 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Victoria E, van Golde LMG, Hostetler KY, Scherphof GL, van Deenan LLM (1971) Some studies on the metabolism of phospholipids in plasma membranes from rat liver. Biochim Biophys Acta 239:443–457Google Scholar
  2. 2.
    Bell RL, Kennerly DA, Stanford N, Majerus PW (1979) Diglyceride lipase: a pathway for arachidonate release from human platelets. Proc Natl Acad Sci USA 76:3238–3241Google Scholar
  3. 3.
    Kennerly DA, Sullivan TJ, Sylwester P, Parker CW (1979) Diacylglycerol metabolism in mast cells: a potential role in membrane fusion and arachidonic acid release. J Exp Med 150:1039–1044Google Scholar
  4. 4.
    Piper PJ, Walker JL (1973) The release of spasmogenic substances from human chopped lung tissue and its inhibition. Br J Pharmacol 47:291–304Google Scholar
  5. 5.
    Adkinson NF Jr, Schulman ES, Newball HH (1983) Anaphylactic release of arachidonic acid metabolites from the lung. In: Newball HH (ed) Immunopharmacology of the Lung. Marcel Dekker, New York, pp 55–72Google Scholar
  6. 6.
    Lewis RA, Soter NA, Diamond PT, Austen KF, Oates JA, Roberts LJ II (1982) Prostaglandin D2 generation after activation of rat and human mast cells with anti-IgE. J Immunol 129:1627–1631Google Scholar
  7. 7.
    Marom Z, Shelhammer JH, Sun F, Kaliner M (1983) Human airway monohydroxy-eicosatetraenoic acid generation and mucus release. J Clin Invest 72:122–127Google Scholar
  8. 8.
    Lewis RA, Austen KF, Drazen JM, Clark DA, Marfat A, Corey EJ (1980) Slow reacting substance of anaphylaxis: identification of leukotrienes C-l and D from human and rat sources. Proc Natl Acad Sci USA 77: 3710–3714Google Scholar
  9. 9.
    Parker CW, Koch D, Huber MM, Falkenhein SF (1980) Formation of the cys-teinyl form of slow reacting substance (leukotriene E4) in human plasma. Biochem Biophys Res Commun 97:1038–1046Google Scholar
  10. 10.
    Fels AOS, Pawlowski NA, Cramer EB, King TKC, Cohn ZA, Scott WA (1982) Human alveolar macrophages produce leukotriene B4. Proc Natl Acad Sci USA 79:7866–7870Google Scholar
  11. Godard P, Damon M, Michel FB, Corey EJ, Austen KF, Lewis RA (1983) Leukotriene B4 production from human alveolar macrophages. Clin Res 31:548AGoogle Scholar
  12. 12.
    Samuelsson B, Goldyne M, Granstrom E, Hamberg M, Hammarstrom S, Malmsten C (1978) Prostaglandins and thromboxanes. Annu Rev Biochem 47:997–1029CrossRefGoogle Scholar
  13. 13.
    Moncada S, Higgs EA, VaneJr (1977) Human arterial and venous tissue generates prostacyclin (prostaglandin x), a potent inhibitor of platelet aggregation. Lancet 1: 18–20Google Scholar
  14. 14.
    Hamberg M, Svensson J, Samuelsson B (1975) Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci USA 72:2994–2998Google Scholar
  15. 15.
    Godard P, Chantreuil J, Damon M, Coupe M, Flandre O, Crastes de Paulet A, Michel FB (1982) Functional assessment of alveolar macrophages: comparison of cells from asthmatics and normal subjects. J Allergy Clin Immunol 70:88–93Google Scholar
  16. 16.
    Lewis RA, Holgate ST, Roberts LJ II, Oates JA, Austen KF (1981) Preferential generation of prostaglandin D2 by rat and human mast cells. In: Becker EL, Simon AS, Austen KF (eds) Biochemistry of the Acute Allergic Reactions, 4th International Symposium. Alan R. Liss, New York, pp 239–254Google Scholar
  17. 17.
    Christ EJ, van Dorp DA (1972) Comparative aspects of prostaglandin biosynthesis in animal tissues. Biochim Biophys Acta 270:537–545Google Scholar
  18. 18.
    Gryglewski RJ, Dembinska-Kiec A, Grodzinska L, Panczcyko B (1976) Differential generation of substances with prostaglandin-like and thromboxane-like activities by guinea pig trachea and lung strips. In: Bouhuys A (ed) Lung Cells in Disease. Elsevier, Amsterdam, pp 289–299Google Scholar
  19. 19.
    Samuelsson B (1983) Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science 220:568–575Google Scholar
  20. 20.
    Lewis RA, Austen KF (1984) The biologically active leukotrienes: biosynthesis, metabolism, receptors, functions, and pharmacology. J Clin Invest 73:889–897Google Scholar
  21. 21.
    MacGlashan DWJr, Schleimer RP, Peters SP, Schulman ES, Adams GK III, Newball HH, Lichtenstein LM (1982) Generation of leukotrienes by purified human lung mast cells. J Clin Invest 70:747–751Google Scholar
  22. 22.
    Borgeat P, Samuelsson B (1979) Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci USA 76:2148–2152Google Scholar
  23. 23.
    Weller PF, Lee CW, Foster DW, Corey EJ, Austen KF, Lewis RA (1983) Generation and metabolism of 5-lipoxygenase pathway leukotrienes by human eosinophils: predominant production of leukotriene C4. Proc Natl Acad Sci USA 80:7626–7630Google Scholar
  24. 24.
    Williams JD, Czop JK, Austen KF (1984) Release of leukotrienes by human monocytes on stimulation of their phagocytic receptor for particulate activators. J Immunol 132:3034–3040Google Scholar
  25. 25.
    Williams JD, Lee TH, Lewis RA, Austen KF (1985) Intracellular retention of the 5-lipoxygenase pathway product, leukotriene B4, by human neutrophils activated with unop-sonized zymosan. J Immunol 134:2624–2630Google Scholar
  26. 26.
    Hamberg M, Samuelsson B (1974) Novel transformation of arachidonic acid in human platelets. Proc Natl Acad Sci USA 71:3400–3404Google Scholar
  27. 27.
    Oates JA (1983) Metabolism of arachidonic acid by the cyclooxygenase pathway in mast cells and by the 15-lipoxygenase pathway in human eosinophils. In: August JT (ed) Biological Response Mediators and Modulators. Academic Press, New York, pp 41–47Google Scholar
  28. 28.
    Serhan CN, Hamberg M, Samuelsson B (1984) Lipoxins: Novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc Natl Acad Sci USA 81:5335–5339Google Scholar
  29. 29.
    Hardy C, Robinson C, Tattersfield A, Holgate ST (1984) The bronchoconstrictor effect of inhaled prostaglandin D2 in normal and asthmatic men. N Engl J Med 311:209–213Google Scholar
  30. 30.
    Flower R, Harvey E, Kingston W (1976) Inflammatory effects of prostaglandin D2 in rat and human skin. Br J Pharmacol 56:229–233Google Scholar
  31. 31.
    Roberts LJ II, Sweetman B, Lewis RA, Austen KF, Oates J (1980) Increased production of prostaglandin D2 in patients with systemic mastocytosis. N Engl J Med 303:1400–1404Google Scholar
  32. 32.
    Goetzl EJ, Weller PF, Valone FH (1979) Biochemical and functional basis of the regulatory and protective roles of the human eosinophil. In: Weissmann G, Samuelsson B, Paoletti R (eds) Advances in Inflammation Research, vol. 1. Raven Press, New York, pp 157–167Google Scholar
  33. 33.
    Weiss JW, Drazen JM, Coles N, McFadden ERJr, Weller P, Corey EJ, Lewis RA, Austen KF (1982) Bronchoconstrictor effects of leukotriene C in human subjects. Science 216:196–198Google Scholar
  34. 34.
    Weiss JW, Drazen JM, McFadden ERJr, Weller P, Corey EJ, Lewis RA, Austen KF (1982) Comparative bronchoconstrictor effects of histamine, leukotriene C and leukotriene D in normal human volunteers. Trans Assoc Am Physicians 95:30–35Google Scholar
  35. 35.
    Krilis S, Lewis RA, Corey EJ, Austen KF (1983) Bioconversion of C-6 sulfidopeptide leukotrienes by the responding guinea pig ileum determines the time course of its contraction. J Clin Invest 71:909–915Google Scholar
  36. 36.
    Krilis S, Lewis RA, Corey EJ, Austen KF (1984) Specific binding of leukotriene C4 to plasma membrane and subcellular receptors of ileal smooth muscle cells. Proc Natl Acad Sci USA 81:4529–4533Google Scholar
  37. 37.
    Krilis S, Lewis RA, Drazen JM, Austen KF (1985) Subclasses of receptors for the sulfidopeptide leukotrienes. In: Braquet P, Garay RP, Frölich JC, Nicosia S (eds) Prostaglandins and Membrane Ion Transport. Raven Press, New York, pp 91–97Google Scholar
  38. 38.
    Hogaboom GK, Mong S, Wu H-L, Crooke S (1983) Peptidoleukotrienes: distinct receptors for leukotrienes C4 and D4 in the guinea pig lung. Biochem Biophys Res Com-mun 116:1136–1143Google Scholar
  39. Schelhamer JH, Marom Z, Sun F, Bach MK, Kaliner M (1982) The effects of arachinoids and leukotrienes on the release of mucus from human airways. Chest 81:36S—37SGoogle Scholar
  40. 40.
    Coles SJ, Neill KH, Reid LM, Austen KF, Nii Y, Corey EJ, Lewis RA (1983) Effects of leukotrienes C4 and D4 on glycoprotein and lysozyme secretion by human bronchial mucosa. Prostaglandins 25:155–170Google Scholar
  41. 41.
    Lewis RA, Drazen JM, Austen KF, Clark DA, Corey EJ (1980) Identification of the C(6)-S-conjugate of leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11 -eis geometry for biological activity. Biochem Biophys Res Commun 96:271–277Google Scholar
  42. 42.
    Dahlen S-E, Bjork J, Hedqvist P, Arfors K-E, Hammarstrom S, Lindgren J-A, Samuelsson B (1981) Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci USA 78:3887–3891Google Scholar
  43. 43.
    Soter NA, Lewis RA, Corey EJ, Austen KF (1983) Local effects of synthetic leukotrienes (LTC4, LTD4, LTE4, and LTB4) in human skin. J Invest Dermatol 80:115–119Google Scholar
  44. 44.
    Drazen JM, Austen KF, Lewis RA, Clark DA, Goto G, Marfat A, Corey EJ (1980) Comparative airway and vascular activities of leukotrienes C-l and D in vivo and in vitro. Proc Natl Acad Sci USA 77:4354–4358Google Scholar
  45. 45.
    Michelassi F, Landa L, Hill RD, Lowenstein E, Watkins WD, Petkau AJ, Zapol WM (1982) Leukotriene D4: a potent coronary artery vasoconstrictor associated with impaired ventricular contraction. Science 217:841–843Google Scholar
  46. 46.
    Pfeffer MA, Pfeffer JM, Lewis RA, Braunwald E, Corey EJ, Austen KF (1983) Systemic hemodynamic effects of leukotrienes C4 and D4 in the rat. Am J Physiol 244: H628–H633Google Scholar
  47. 47.
    Badr KF, Baylis C, Pfeffer JM, Pfeffer MA, Soberman RJ, Lewis RA, Austen KF, Corey EJ, Brenner BM (1984) Renal and systemic hemodynamic responses to intravenous infusion of leukotriene C4 in the rat. Circ Res 54:492–499Google Scholar
  48. 48.
    Stenmark KR, James SL, Voelkel NF, Toews WH, Reeves JT, Murphy RC (1983) Leukotriene C4 and D4 in neonates with hypoxemia and pulmonary hypertension. N Engl J Med 309:77–80Google Scholar
  49. 49.
    Hoover R, Karnovsky MJ, Austen KF, Corey EJ, Lewis RA (1984) Leukotriene B4 action on endothelium mediates augmented neutrophil/endothelial adhesion. Proc Natl Acad Sci USA 81:2191–2193Google Scholar
  50. 50.
    Atluru D, Goodwin JS (1984) Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; LTB4 induces an OKT8(+), radiosensitive suppressor cell from resting human OKT8(-) T cells. J Clin Invest 74:1442–1450Google Scholar
  51. 51.
    Payan DG, Goetzl EJ (1983) Specific suppression of human T lymphocyte function by leukotriene B4. J Immunol 131:551–553Google Scholar
  52. 52.
    Rola-Plezczynski MP, Borgeat P, Sirois P (1982) Leukotriene B4 induces human suppressor lymphocytes. Biochem Biophys Res Commun 198:1531–1534Google Scholar
  53. 53.
    VaneJr (1978) Inhibitors of prostaglandin, prostacyclin, and thromboxane synthesis. Adv Prostaglandin Thromboxane Leukotriene Res 4:27–44Google Scholar
  54. 54.
    Ham EA, Soderman DD, Zanetti ME, Dougherty HW, McCauley E, Kuehl FAJr (1983) Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils. Proc Natl Acad Sci USA 80: 4349–4353Google Scholar
  55. 55.
    Razin E, Romeo LC, Krilis S, Liu F-T, Lewis RA, Corey EJ, Austen KF (1984) An analysis of the relationship between 5-lipoxygenase product generation and the secretion of preformed mediators from mouse bone marrow-derived mast cells. J Immunol 133: 938–945Google Scholar
  56. Bach MK, BrashlerJr, Smith HW, Fitz-patrick FA, Sun FF, Maguire JC (1982) 6,9- deepoxy-6,9-(phenylimino)-Zl6,8-prostaglan-din li (U-60,257), a new inhibitor of leukotriene C and D synthesis: in vitro studies. Prostaglandins 23:759–771Google Scholar
  57. 57.
    Goldman DW, Goetzl EJ (1982) Specific binding of leukotriene B4 to receptors on human polymorphonuclear leukocytes. J Immunol 129:1600–1604Google Scholar
  58. 58.
    Ballermann BJ, Lewis RA, Corey EJ, Austen KF, Brenner BM (1985) Identification and characterization of leukotriene C4 receptors in isolated rat renal glomeruli. Circ Res 56:324–330Google Scholar
  59. 59.
    Murphy RC, Pickett WC, Culp BR, Lands WEM (1981) Tetraene and pentaene leukotrienes: selective production from murine mastocytoma cells after dietary manipulation. Prostaglandins 22:613–619Google Scholar
  60. 60.
    Leitch AG, Lee TH, Ringel EW, Prickett JD, Robinson DR, Pyne SG, Austen KF, Lewis RA (1984) Immunologically induced generation of tetraene and pentaene leukotrienes in the peritoneal cavities of menhaden-fed rats. J Immunol 132:2559–2565Google Scholar
  61. 61.
    Lee TH, Mencia-Huerta J-M, Shih C, Corey EJ, Lewis RA, Austen KF (1984) Characterization and biological properties of 5,12-dihy-droxy derivatives of eicosapentaenoic acid, including leukotriene B5 and the double lipoxygenase product. J Biol Chem 259:2383–2389Google Scholar
  62. 62.
    Lee TH, Mencia-Huerta J-M, Shih C, Corey EJ, Lewis RA, Austen KF (1984) Effects of exogenous arachidonic, eicosapentaenoic, and docosahexaenoic acids on the generation of 5-lipoxygenase pathway products by ionophore-activated human neutrophils. J Clin Invest 74:1922–1933Google Scholar
  63. 63.
    Hirata F, Notsu Y, Iwata M, Parente L, diRosa M, Flower RJ (1982) Identification of several species of phospholipase inhibiting protein(s) by radioimmunoassay for lipomo-dulin. Biochem Biophys Res Commun 109:223–230Google Scholar
  64. 64.
    Hirata F, Iwati M (1983) Role of lipomo-dulin, a phospholipase inhibitory protein in immunoregulation by thymocytes. J Immunol 130:1930–1936Google Scholar
  65. 65.
    Rothhut B, Russo-Marie F, Wood J, diRosa M, Flower RJ (1983) Further characterization of the glucocorticoid-induced anti-phospholipase protein ‘renocortin.’ Biochem Biophys Res Commun 117:878–884Google Scholar
  66. 66.
    Saed SA, McDonald-Gibson WJ, Cuthbert J, Copas JL, Schneider C, Gardiner PJ, Butt NM, Collier HO J (1977) Endogenous inhibitor of prostaglandin synthetase. Nature 270:32–36Google Scholar
  67. 67.
    Moore PK, HoultJrS (1980) Anti-inflammatory steroids reduce tissue PG synthetase activity and enhance PG breakdown. Nature 288:269–270Google Scholar
  68. 68.
    Lewis RA, Robin J-L, Austen KF (1985) Pharmacologic regulation of mediator generation and release from the murine bone mar-row-derived mast cell. Int Arch Allergy Appl Immunol 77:137–143Google Scholar
  69. Godard P, Damon M, Michel FB, Craste de Paulet A, Corey EJ, Ciliberti M, Lewis RA (submitted for publication) Generation of leukotriene B4, sulfidopeptide leukotrienes, and selected cyclooxygenase products from alveolar macrophages of normal and asthmatic individualsGoogle Scholar
  70. 70.
    Williams JD, Lee TH, Lewis RA, Austen KF (1985) Intracellular retention of the 5-lipoxygenase pathway product, leukotriene B4 by human neutrophils activated with opsonized zymosan. J Immunol 134:2624–2630Google Scholar

Copyright information

© Springer-Verlag, Berlin Heidelberg 1987

Authors and Affiliations

  • R. A. Lewis
  • J.-L. Robin

There are no affiliations available

Personalised recommendations