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. 1983 Oct;113(1):75–84.

Spasmogenic properties of platelet-activating factor: evidence for a direct mechanism in the contractile response of pulmonary tissues.

N P Stimler, J T O'Flaherty
PMCID: PMC1916293  PMID: 6624879

Abstract

Platelet-activating factor (1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine; PAF) induces a specific, dose-dependent contraction of guinea pig lung parenchymal strips with an ED50 value of 10(-9) M. The smooth muscle contractile activity of PAF in this system was not effected by the H1-blocking antihistamine, pyrilamine (10(-6) M), the prostaglandin synthesis inhibitors, indomethacin (10(-5) M), aspirin (10(-4) M), or sulfinpyrazone (5 X 10(-4) M), the leukotriene synthesis inhibitor, nordihydroguaiaretic acid (NDGA; 10(-5) M), the leukotriene antagonist FPL 55712 (10(-6) M) or the inhibitor of arachidonic acid metabolism, eicosatetraynoic acid (ETYA; 2 X 10(-5) M). The role of platelets in this system was also investigated. PAF-mediated contractions were not attenuated following platelet depletion using nitrogen mustard, nor were they augmented by the addition of exogenous platelets. Furthermore, isolated platelets incubated with PAF did not release stable substances spasmogenic for lung parenchymal strips. Finally, contractile activity of PAF was demonstrated in lung parenchymal strips from rats, a species whose platelets are insensitive to PAF at elevated concentrations. Taken together, these data show that PAF contracts smooth muscle of guinea pig lung parenchyma independently of endogenous histamine, arachidonic acid metabolites, or platelets trapped within the pulmonary vasculature. It is concluded, therefore, that PAF may act directly on contractile cells of the lung.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnoux B., Duval D., Benveniste J. Release of platelet-activating factor (PAF-acether) from alveolar macrophages by the calcium ionophore A23187 and phagocytosis. Eur J Clin Invest. 1980 Dec;10(6):437–441. doi: 10.1111/j.1365-2362.1980.tb02082.x. [DOI] [PubMed] [Google Scholar]
  2. Benveniste J., Henson P. M., Cochrane C. G. Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor. J Exp Med. 1972 Dec 1;136(6):1356–1377. doi: 10.1084/jem.136.6.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benveniste J. Platelet-activating factor, a new mediator of anaphylaxis and immune complex deposition from rabbit and human basophils. Nature. 1974 Jun 7;249(457):581–582. doi: 10.1038/249581a0. [DOI] [PubMed] [Google Scholar]
  4. Benveniste J., Tencé M., Varenne P., Bidault J., Boullet C., Polonsky J. Semi-synthèse et structure proposée du facteur activant les plaquettes (P.A.F.): PAF-acether, un alkyl ether analogue de la lysophosphatidylcholine. C R Seances Acad Sci D. 1979 Nov 26;289(14):1037–1040. [PubMed] [Google Scholar]
  5. Chignard M., Le Couedic J. P., Tence M., Vargaftig B. B., Benveniste J. The role of platelet-activating factor in platelet aggregation. Nature. 1979 Jun 28;279(5716):799–800. doi: 10.1038/279799a0. [DOI] [PubMed] [Google Scholar]
  6. Chilton F. H., O'Flaherty J. T., Walsh C. E., Thomas M. J., Wykle R. L., DeChatelet L. R., Waite B. M. Platelet activating factor. Stimulation of the lipoxygenase pathway in polymorphonuclear leukocytes by 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine. J Biol Chem. 1982 May 25;257(10):5402–5407. [PubMed] [Google Scholar]
  7. Demopoulos C. A., Pinckard R. N., Hanahan D. J. Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators). J Biol Chem. 1979 Oct 10;254(19):9355–9358. [PubMed] [Google Scholar]
  8. Halonen M., Palmer J. D., Lohman I. C., McManus L. M., Pinckard R. N. Respiratory and circulatory alterations induced by acetyl glyceryl ether phosphorylcholine, a mediator of IgE anaphylaxis in the rabbit. Am Rev Respir Dis. 1980 Dec;122(6):915–924. doi: 10.1164/arrd.1980.122.6.915. [DOI] [PubMed] [Google Scholar]
  9. Hamberg M., Svensson J., Hedqvist P., Strandberg K., Samuelsson B. Involvement of endoperoxides and thromboxanes in anaphylactic reactions. Adv Prostaglandin Thromboxane Res. 1976;1:495–501. [PubMed] [Google Scholar]
  10. Hamberg M., Svensson J., Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994–2998. doi: 10.1073/pnas.72.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hanahan D. J., Demopoulos C. A., Liehr J., Pinckard R. N. Identification of platelet activating factor isolated from rabbit basophils as acetyl glyceryl ether phosphorylcholine. J Biol Chem. 1980 Jun 25;255(12):5514–5516. [PubMed] [Google Scholar]
  12. Henson P. M., Pinckard R. N. Basophil-derived platelet-activating factor (PAF) as an in vivo mediator of acute allergic reactions: demonstration of specific desensitization of platelets to PAF during IgE-induced anaphylaxis in the rabbit. J Immunol. 1977 Dec;119(6):2179–2184. [PubMed] [Google Scholar]
  13. Lewis R. A., Austen K. F., Drazen J. M., Clark D. A., Marfat A., Corey E. J. Slow reacting substances of anaphylaxis: identification of leukotrienes C-1 and D from human and rat sources. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3710–3714. doi: 10.1073/pnas.77.6.3710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lin A. H., Morton D. R., Gorman R. R. Acetyl glyceryl ether phosphorylcholine stimulates leukotriene B4 synthesis in human polymorphonuclear leukocytes. J Clin Invest. 1982 Nov;70(5):1058–1065. doi: 10.1172/JCI110693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lotner G. Z., Lynch J. M., Betz S. J., Henson P. M. Human neutrophil-derived platelet activating factor. J Immunol. 1980 Feb;124(2):676–684. [PubMed] [Google Scholar]
  16. Lynch J. M., Lotner G. Z., Betz S. J., Henson P. M. The release of a platelet-activating factor by stimulated rabbit neutrophils. J Immunol. 1979 Sep;123(3):1219–1226. [PubMed] [Google Scholar]
  17. Marcus A. J., Safier L. B., Ullman H. L., Wong K. T., Broekman M. J., Weksler B. B., Kaplan K. L. Effects of acetyl glyceryl ether phosphorylcholine on human platelet function in vitro. Blood. 1981 Nov;58(5):1027–1031. [PubMed] [Google Scholar]
  18. Mencia-Huerta J. M., Hadji L., Benveniste J. Release of a slow-reacting substance from rabbit platelets. J Clin Invest. 1981 Dec;68(6):1586–1591. doi: 10.1172/JCI110413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. O'Flaherty J. T. Lipid mediators of inflammation and allergy. Lab Invest. 1982 Oct;47(4):314–329. [PubMed] [Google Scholar]
  20. O'Flaherty J. T., Miller C. H., Lewis J. C., Wykle R. L., Bass D. A., McCall C. E., Waite M., DeChatelet L. R. Neutrophil responses to platelet-activating factor. Inflammation. 1981 Sep;5(3):193–201. doi: 10.1007/BF00914443. [DOI] [PubMed] [Google Scholar]
  21. Pinckard R. N., Farr R. S., Hanahan D. J. Physicochemical and functional identity of rabbit platelet-activating factor (PAF) released in vivo during IgE anaphylaxis with PAF released in vitro from IgE sensitized basophils. J Immunol. 1979 Oct;123(4):1847–1857. [PubMed] [Google Scholar]
  22. Rouser G., Siakotos A. N., Fleischer S. Quantitative analysis of phospholipids by thin-layer chromatography and phosphorus analysis of spots. Lipids. 1966 Jan;1(1):85–86. doi: 10.1007/BF02668129. [DOI] [PubMed] [Google Scholar]
  23. Shaw J. O., Printz M. P., Hirabayashi K., Henson P. M. Role of prostaglandin synthesis in rabbit platelet activation induced by basophil-derived platelet-activating factor. J Immunol. 1978 Nov;121(5):1939–1945. [PubMed] [Google Scholar]
  24. Stimler N. P., Bach M. K., Bloor C. M., Hugli T. E. Release of leukotrienes from guinea pig lung stimulated by C5ades Arg anaphylatoxin. J Immunol. 1982 May;128(5):2247–2252. [PubMed] [Google Scholar]
  25. Stimler N. P., Bloor C. M., Hugli T. E. C3a-induced contraction of guinea pig lung parenchyma: role of cyclooxygenase metabolites. Immunopharmacology. 1983 Feb;5(3):251–257. doi: 10.1016/0162-3109(83)90031-0. [DOI] [PubMed] [Google Scholar]
  26. Stimler N. P., Bloor C. M., Hugli T. E., Wykle R. L., McCall C. E., O'Flaherty J. T. Anaphylactic actions of platelet-activating factor. Am J Pathol. 1981 Oct;105(1):64–69. [PMC free article] [PubMed] [Google Scholar]
  27. Stimler N. P., Hugli T. E., Bloor C. M. Pulmonary injury induced by C3a and C5a anaphylatoxins. Am J Pathol. 1980 Aug;100(2):327–348. [PMC free article] [PubMed] [Google Scholar]
  28. Tencé V., Polonsky J., Le Couedic J. P., Benveniste M. J. Release, purification, and characterization of platelet-activating factor (PAF). Biochimie. 1980;62(4):251–259. doi: 10.1016/s0300-9084(80)80399-3. [DOI] [PubMed] [Google Scholar]
  29. Vargaftig B. B., Chignard M., Benveniste J., Lefort J., Wal F. Background and present status of research on platelet-activating factor (PAF-acether). Ann N Y Acad Sci. 1981;370:119–137. doi: 10.1111/j.1749-6632.1981.tb29727.x. [DOI] [PubMed] [Google Scholar]
  30. Vargaftig B. B., Lefort J., Chignard M., Benveniste J. Platelet-activating factor induces a platelet-dependent bronchoconstriction unrelated to the formation of prostaglandin derivatives. Eur J Pharmacol. 1980 Jul 25;65(2-3):185–192. doi: 10.1016/0014-2999(80)90391-x. [DOI] [PubMed] [Google Scholar]

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