Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1993 May;61(5):1996–2002. doi: 10.1128/iai.61.5.1996-2002.1993

Bacteria induce release of platelet-activating factor (PAF) from polymorphonuclear neutrophil granulocytes: possible role for PAF in pathogenesis of experimentally induced bacterial pneumonia.

A Makristathis 1, F Stauffer 1, S M Feistauer 1, A Georgopoulos 1
PMCID: PMC280794  PMID: 8478087

Abstract

The role of platelet-activating factor (PAF) as mediator of the endotoxin shock and endotoxin-dependent tissue injury has been examined. The ability of opsonized bacteria to stimulate the release of PAF from human polymorphonuclear neutrophil granulocytes was evaluated by measuring both the activity and the amount of the mediator released in the supernatant of the cell-bacteria reaction in vitro. There was no significant difference between gram-positive and gram-negative bacteria in the ability to release PAF from neutrophils. However, preincubation of the cells with the specific PAF receptor antagonist WEB 2170 decreased release of PAF from the cells. Furthermore, a possible protective effect of the PAF antagonist was examined during experimentally induced pneumonia with Klebsiella pneumoniae in NMRI mice. Oral treatment of mice with WEB 2170, followed by infection with the microorganisms, resulted in a considerable increase in the animals' survival (53 to 73%) compared with the control group (40%); this increase corresponded with a decrease in the CFU per gram of lung tissue. These findings indicate an important role of PAF in the pathogenesis of pneumonia in mice.

Full text

PDF
1996

Selected References

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

  1. Benveniste J., Boullet C., Brink C., Labat C. The actions of Paf-acether (platelet-activating factor) on guinea-pig isolated heart preparations. Br J Pharmacol. 1983 Sep;80(1):81–83. doi: 10.1111/j.1476-5381.1983.tb11052.x. [DOI] [PMC free article] [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. Block L. H., Abraham W. M., Groscurth P., Qiao B. Y., Perruchoud A. P. Platelet-activating factor (PAF)-dependent biochemical, morphologic, and physiologic responses of human platelets: demonstration of translocation of protein kinase C associated with protein phosphorylation. Am J Respir Cell Mol Biol. 1989 Oct;1(4):277–288. doi: 10.1165/ajrcmb/1.4.277. [DOI] [PubMed] [Google Scholar]
  4. Braquet P., Paubert-Braquet M., Bourgain R. H., Bussolino F., Hosford D. PAF/cytokine auto-generated feedback networks in microvascular immune injury: consequences in shock, ischemia and graft rejection. J Lipid Mediat. 1989 Mar-Apr;1(2):75–112. [PubMed] [Google Scholar]
  5. Camussi G., Aglietta M., Coda R., Bussolino F., Piacibello W., Tetta C. Release of platelet-activating factor (PAF) and histamine. II. The cellular origin of human PAF: monocytes, polymorphonuclear neutrophils and basophils. Immunology. 1981 Feb;42(2):191–199. [PMC free article] [PubMed] [Google Scholar]
  6. Camussi G., Tetta C., Bussolino F., Caligaris Cappio F., Coda R., Masera C., Segoloni G. Mediators of immune-complex-induced aggregation of polymorphonuclear neutrophils. II. Platelet-activating factor as the effector substance of immune-induced aggregation. Int Arch Allergy Appl Immunol. 1981;64(1):25–41. doi: 10.1159/000232671. [DOI] [PubMed] [Google Scholar]
  7. Casals-Stenzel J. Effects of WEB 2086, a novel antagonist of platelet activating factor, in active and passive anaphylaxis. Immunopharmacology. 1987 Apr;13(2):117–124. doi: 10.1016/0162-3109(87)90048-8. [DOI] [PubMed] [Google Scholar]
  8. Casals-Stenzel J., Franke J., Friedrich T., Lichey J. Bronchial and vascular effects of Paf in the rat isolated lung are completely blocked by WEB 2086, a novel specific Paf antagonist. Br J Pharmacol. 1987 Aug;91(4):799–802. doi: 10.1111/j.1476-5381.1987.tb11278.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang S. W., Fernyak S., Voelkel N. F. Beneficial effect of a platelet-activating factor antagonist, WEB 2086, on endotoxin-induced lung injury. Am J Physiol. 1990 Jan;258(1 Pt 2):H153–H158. doi: 10.1152/ajpheart.1990.258.1.H153. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Darius H., Lefer D. J., Smith J. B., Lefer A. M. Role of platelet-activating factor-acether in mediating guinea pig anaphylaxis. Science. 1986 Apr 4;232(4746):58–60. doi: 10.1126/science.3082008. [DOI] [PubMed] [Google Scholar]
  12. Denizot Y., Dassa E., Kim H. Y., Bossant M. J., Salem N., Jr, Thomas Y., Benveniste J. Synthesis of paf-acether from exogenous precursors by the prokaryote Escherichia coli. FEBS Lett. 1989 Jan 16;243(1):13–16. doi: 10.1016/0014-5793(89)81207-4. [DOI] [PubMed] [Google Scholar]
  13. Doebber T. W., Wu M. S. Platelet-activating factor (PAF) stimulates the PAF-synthesizing enzyme acetyl-CoA:1-alkyl-sn-glycero-3-phosphocholine O2-acetyltransferase and PAF synthesis in neutrophils. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7557–7561. doi: 10.1073/pnas.84.21.7557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Etienne A., Hecquet F., Soulard C., Touvay C., Clostre F., Braquet P. The relative role of PAF-acether and icosanoids in septic shock. Pharmacol Res Commun. 1986 Aug;18 (Suppl):71–79. doi: 10.1016/0031-6989(86)90040-8. [DOI] [PubMed] [Google Scholar]
  15. Findlay S. R., Lichtenstein L. M., Hanahan D. J., Pinckard R. N. Contraction of guinea pig ileal smooth muscle by acetyl glyceryl ether phosphorylcholine. Am J Physiol. 1981 Sep;241(3):C130–C133. doi: 10.1152/ajpcell.1981.241.3.C130. [DOI] [PubMed] [Google Scholar]
  16. Georgopoulos A. Tiefgefriekonservierung von Pilzen in flüssigem Stickstoff als Grundlage für standardisierte Inokula. Mykosen. 1978 Jan;21(1):19–23. [PubMed] [Google Scholar]
  17. Heuer H. O., Casals-Stenzel J., Muacevic G., Weber K. H. Pharmacologic activity of bepafant (WEB 2170), a new and selective hetrazepinoic antagonist of platelet activating factor. J Pharmacol Exp Ther. 1990 Dec;255(3):962–968. [PubMed] [Google Scholar]
  18. Humphrey D. M., McManus L. M., Hanahan D. J., Pinckard R. N. Morphologic basis of increased vascular permeability induced by acetyl glyceryl ether phosphorylcholine. Lab Invest. 1984 Jan;50(1):16–25. [PubMed] [Google Scholar]
  19. Humphrey D. M., McManus L. M., Satouchi K., Hanahan D. J., Pinckard R. N. Vasoactive properties of acetyl glyceryl ether phosphorylcholine and analogues. Lab Invest. 1982 Apr;46(4):422–427. [PubMed] [Google Scholar]
  20. Kasimir S., Schönfeld W., Alouf J. E., König W. Effect of Staphylococcus aureus delta-toxin on human granulocyte functions and platelet-activating-factor metabolism. Infect Immun. 1990 Jun;58(6):1653–1659. doi: 10.1128/iai.58.6.1653-1659.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Lopez Diez F., Nieto M. L., Fernandez-Gallardo S., Gijon M. A., Sanchez Crespo M. Occupancy of platelet receptors for platelet-activating factor in patients with septicemia. J Clin Invest. 1989 May;83(5):1733–1740. doi: 10.1172/JCI114074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Rehm S. R., Gross G. N., Pierce A. K. Early bacterial clearance from murine lungs. Species-dependent phagocyte response. J Clin Invest. 1980 Aug;66(2):194–199. doi: 10.1172/JCI109844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Robertson D. A., Wang D. Y., Lee C. O., Levi R. Negative inotropic effect of platelet-activating factor: association with a decrease in intracellular sodium activity. J Pharmacol Exp Ther. 1988 Apr;245(1):124–128. [PubMed] [Google Scholar]
  26. Robinson M., Snyder F. Metabolism of platelet-activating factor by rat alveolar macrophages: lyso-PAF as an obligatory intermediate in the formation of alkylarachidonoyl glycerophosphocholine species. Biochim Biophys Acta. 1985 Oct 23;837(1):52–56. doi: 10.1016/0005-2760(85)90084-0. [DOI] [PubMed] [Google Scholar]
  27. Rubin A. H., Smith L. J., Patterson R. The bronchoconstrictor properties of platelet-activating factor in humans. Am Rev Respir Dis. 1987 Nov;136(5):1145–1151. doi: 10.1164/ajrccm/136.5.1145. [DOI] [PubMed] [Google Scholar]
  28. Shaw J. O., Pinckard R. N., Ferrigni K. S., McManus L. M., Hanahan D. J. Activation of human neutrophils with 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycerol-3-phosphorylcholine (platelet activating factor). J Immunol. 1981 Sep;127(3):1250–1255. [PubMed] [Google Scholar]
  29. Sisson J. H., Prescott S. M., McIntyre T. M., Zimmerman G. A. Production of platelet-activating factor by stimulated human polymorphonuclear leukocytes. Correlation of synthesis with release, functional events, and leukotriene B4 metabolism. J Immunol. 1987 Jun 1;138(11):3918–3926. [PubMed] [Google Scholar]
  30. Valone F. H., Goetzl E. J. Specific binding by human polymorphonuclear leucocytes of the immunological mediator 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycero-3-phosphorylcholine. Immunology. 1983 Jan;48(1):141–149. [PMC free article] [PubMed] [Google Scholar]
  31. Worthen G. S., Seccombe J. F., Clay K. L., Guthrie L. A., Johnston R. B., Jr The priming of neutrophils by lipopolysaccharide for production of intracellular platelet-activating factor. Potential role in mediation of enhanced superoxide secretion. J Immunol. 1988 May 15;140(10):3553–3559. [PubMed] [Google Scholar]
  32. Yasaka T., Boxer L. A., Baehner R. L. Monocyte aggregation and superoxide anion release in response to formyl-methionyl-leucyl-phenylalanine (FMLP) and platelet-activating factor (PAF). J Immunol. 1982 May;128(5):1939–1944. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES