Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 May;83(5):1733–1740. doi: 10.1172/JCI114074

Occupancy of platelet receptors for platelet-activating factor in patients with septicemia.

F Lopez Diez 1, M L Nieto 1, S Fernandez-Gallardo 1, M A Gijon 1, M Sanchez Crespo 1
PMCID: PMC303883  PMID: 2540221

Abstract

The possible involvement of platelet-activating factor (PAF) in the pathogenesis of endotoxemia, was investigated by using a binding assay to patients' platelets, complemented with the extraction and chemical characterization of PAF obtained from patients' platelets. Platelets from 12 human volunteers had 281 +/- 63 freely accessible high affinity binding sites (PAF-receptors) per platelet; whereas this number was of 49 +/- 37 PAF-receptors per platelet, n = 14 samples, P less than 0.01, in a group of 13 patients with positive blood culture. A group of patients with respiratory or cardiovascular disturbances and negative blood culture had 253 +/- 74, accessible receptors per platelet (n = 19 samples from 16 patients, P less than 0.01 as compared to septic patients, which was not significantly different when compared to control individuals). Patients with sepsis possessed significant amounts of PAF associated to their platelets, whereas this mediator could not be isolated from platelets of patients with respiratory or cardiovascular disturbances and negative blood culture, nor from platelets of control individuals. PAF was also assayed in whole blood samples and found at high concentrations in sepsis patients. These data indicate that occupancy of PAF receptors in combination with high amounts of platelet-associated PAF, is a common finding in patients with sepsis.

Full text

PDF
1733

Selected References

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

  1. Adnot S., Lefort J., Lagente V., Braquet P., Vargaftig B. B. Interference of BN 52021, a PAF-acether antagonist, with endotoxin-induced hypotension in the guinea-pig. Pharmacol Res Commun. 1986 Aug;18 (Suppl):197–200. doi: 10.1016/0031-6989(86)90052-4. [DOI] [PubMed] [Google Scholar]
  2. Alam I., Smith J. B., Silver M. J. Metabolism of platelet-activating factor by blood platelets and plasma. Lipids. 1983 Aug;18(8):534–538. doi: 10.1007/BF02535393. [DOI] [PubMed] [Google Scholar]
  3. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  4. Beijer L., Botting J., Crook P., Oyekan A. O., Page C. P., Rylander R. The involvement of platelet activating factor in endotoxin-induced pulmonary platelet recruitment in the guinea-pig. Br J Pharmacol. 1987 Dec;92(4):803–808. doi: 10.1111/j.1476-5381.1987.tb11384.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benveniste J., Nunez D., Duriez P., Korth R., Bidault J., Fruchart J. C. Preformed PAF-acether and lyso PAF-acether are bound to blood lipoproteins. FEBS Lett. 1988 Jan 4;226(2):371–376. doi: 10.1016/0014-5793(88)81456-x. [DOI] [PubMed] [Google Scholar]
  6. Blank M. L., Snyder F., Byers L. W., Brooks B., Muirhead E. E. Antihypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochem Biophys Res Commun. 1979 Oct 29;90(4):1194–1200. doi: 10.1016/0006-291x(79)91163-x. [DOI] [PubMed] [Google Scholar]
  7. Blank M. L., Snyder F. Improved high-performance liquid chromatographic method for isolation of platelet-activating factor from other phospholipids. J Chromatogr. 1983 Apr 8;273(2):415–420. doi: 10.1016/s0378-4347(00)80963-9. [DOI] [PubMed] [Google Scholar]
  8. Bone R. C., Fisher C. J., Jr, Clemmer T. P., Slotman G. J., Metz C. A., Balk R. A. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med. 1987 Sep 10;317(11):653–658. doi: 10.1056/NEJM198709103171101. [DOI] [PubMed] [Google Scholar]
  9. Camussi G., Aglietta M., Malavasi F., Tetta C., Piacibello W., Sanavio F., Bussolino F. The release of platelet-activating factor from human endothelial cells in culture. J Immunol. 1983 Nov;131(5):2397–2403. [PubMed] [Google Scholar]
  10. Camussi G., Tetta C., Deregibus M. C., Bussolino F., Segoloni G., Vercellone A. Platelet-activating factor (PAF) in experimentally-induced rabbit acute serum sickness: role of basophil-derived PAF in immune complex deposition. J Immunol. 1982 Jan;128(1):86–94. [PubMed] [Google Scholar]
  11. Caramelo C., Fernández-Gallardo S., Marín-Cao D., Iñarrea P., Santos J. C., López-Novoa J. M., Sanchez Crespo M. Presence of platelet-activating factor in blood from humans and experimental animals. Its absence in anephric individuals. Biochem Biophys Res Commun. 1984 May 16;120(3):789–796. doi: 10.1016/s0006-291x(84)80176-x. [DOI] [PubMed] [Google Scholar]
  12. Caramelo C., Fernández-Gallardo S., Santos J. C., Iñarrea P., Sánchez-Crespo M., López-Novoa J. M., Hernando L. Increased levels of platelet-activating factor in blood from patients with cirrhosis of the liver. Eur J Clin Invest. 1987 Feb;17(1):7–11. doi: 10.1111/j.1365-2362.1987.tb01218.x. [DOI] [PubMed] [Google Scholar]
  13. Chang S. W., Feddersen C. O., Henson P. M., Voelkel N. F. Platelet-activating factor mediates hemodynamic changes and lung injury in endotoxin-treated rats. J Clin Invest. 1987 May;79(5):1498–1509. doi: 10.1172/JCI112980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Doebber T. W., Wu M. S., Robbins J. C., Choy B. M., Chang M. N., Shen T. Y. Platelet activating factor (PAF) involvement in endotoxin-induced hypotension in rats. Studies with PAF-receptor antagonist kadsurenone. Biochem Biophys Res Commun. 1985 Mar 29;127(3):799–808. doi: 10.1016/s0006-291x(85)80014-0. [DOI] [PubMed] [Google Scholar]
  17. Grandel K. E., Farr R. S., Wanderer A. A., Eisenstadt T. C., Wasserman S. I. Association of platelet-activating factor with primary acquired cold urticaria. N Engl J Med. 1985 Aug 15;313(7):405–409. doi: 10.1056/NEJM198508153130702. [DOI] [PubMed] [Google Scholar]
  18. Heffner J. E., Sahn S. A., Repine J. E. The role of platelets in the adult respiratory distress syndrome. Culprits or bystanders? Am Rev Respir Dis. 1987 Feb;135(2):482–492. doi: 10.1164/arrd.1987.135.2.482. [DOI] [PubMed] [Google Scholar]
  19. Heffner J. E., Shoemaker S. A., Canham E. M., Patel M., McMurtry I. F., Morris H. G., Repine J. E. Acetyl glyceryl ether phosphorylcholine-stimulated human platelets cause pulmonary hypertension and edema in isolated rabbit lungs. Role of thromboxane A2. J Clin Invest. 1983 Feb;71(2):351–357. doi: 10.1172/JCI110776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Henson P. M. Activation and desensitization of platelets by platelet-activating factor (PAF) derived from IgE-sensitized basophils. I. Characteristics of the secretory response. J Exp Med. 1976 Apr 1;143(4):937–952. doi: 10.1084/jem.143.4.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hwang S. B., Lam M. H., Shen T. Y. Specific binding sites for platelet activating factor in human lung tissues. Biochem Biophys Res Commun. 1985 Apr 30;128(2):972–979. doi: 10.1016/0006-291x(85)90142-1. [DOI] [PubMed] [Google Scholar]
  22. Iñarrea P., Alonso F., Sanchez-Crespo M. Platelet-activating factor: an effector substance of the vasopermeability changes induced by the infusion of immune aggregates in the mouse. Immunopharmacology. 1983 Jun;6(1):7–14. doi: 10.1016/0162-3109(83)90011-5. [DOI] [PubMed] [Google Scholar]
  23. Iñarrea P., Gomez-Cambronero J., Nieto M., Crespo M. S. Characteristics of the binding of platelet-activating factor to platelets of different animal species. Eur J Pharmacol. 1984 Oct 15;105(3-4):309–315. doi: 10.1016/0014-2999(84)90623-x. [DOI] [PubMed] [Google Scholar]
  24. Iñarrea P., Gomez-Cambronero J., Pascual J., Ponte M. C., Hernando L., Sánchez-Crespo M. Synthesis of PAF-acether and blood volume changes in gram-negative sepsis. Immunopharmacology. 1985 Feb;9(1):45–52. doi: 10.1016/0162-3109(85)90046-3. [DOI] [PubMed] [Google Scholar]
  25. Jackson C. V., Schumacher W. A., Kunkel S. L., Driscoll E. M., Lucchesi B. R. Platelet-activating factor and the release of a platelet-derived coronary artery vasodilator substance in the canine. Circ Res. 1986 Feb;58(2):218–229. doi: 10.1161/01.res.58.2.218. [DOI] [PubMed] [Google Scholar]
  26. Jackson E. M., Mott G. E., Hoppens C., McManus L. M., Weintraub S. T., Ludwig J. C., Pinckard R. N. High performance liquid chromatography of platelet-activating factors. J Lipid Res. 1984 Jul;25(7):753–757. [PubMed] [Google Scholar]
  27. Kloprogge E., Akkerman J. W. Binding kinetics of PAF-acether (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) to intact human platelets. Biochem J. 1984 Nov 1;223(3):901–909. doi: 10.1042/bj2230901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. McIntyre T. M., Zimmerman G. A., Satoh K., Prescott S. M. Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate. J Clin Invest. 1985 Jul;76(1):271–280. doi: 10.1172/JCI111957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. McManus L. M., Hanahan D. J., Demopoulos C. A., Pinckard R. N. Pathobiology of the intravenous infusion of acetyl glyceryl ether phosphorylcholine (AGEPC), a synthetic platelet-activating factor (PAF), in the rabbit. J Immunol. 1980 Jun;124(6):2919–2924. [PubMed] [Google Scholar]
  31. Miwa M., Hill C., Kumar R., Sugatani J., Olson M. S., Hanahan D. J. Occurrence of an endogenous inhibitor of platelet-activating factor in rat liver. J Biol Chem. 1987 Jan 15;262(2):527–530. [PubMed] [Google Scholar]
  32. Morrison D. C., Ulevitch R. J. The effects of bacterial endotoxins on host mediation systems. A review. Am J Pathol. 1978 Nov;93(2):526–618. [PMC free article] [PubMed] [Google Scholar]
  33. Nakayama R., Yasuda K., Saito K. Existence of endogenous inhibitors of platelet-activating factor (PAF) with PAF in rat uterus. J Biol Chem. 1987 Sep 25;262(27):13174–13179. [PubMed] [Google Scholar]
  34. Nieto M. L., Velasco S., Sanchez Crespo M. Biosynthesis of platelet-activating factor in human polymorphonuclear leukocytes. Involvement of the cholinephosphotransferase pathway in response to the phorbol esters. J Biol Chem. 1988 Feb 15;263(5):2217–2222. [PubMed] [Google Scholar]
  35. Patton G. M., Fasulo J. M., Robins S. J. Separation of phospholipids and individual molecular species of phospholipids by high-performance liquid chromatography. J Lipid Res. 1982 Jan;23(1):190–196. [PubMed] [Google Scholar]
  36. Pieroni G., Hanahan D. J. Metabolic behavior of acetyl glyceryl ether phosphorylcholine on interaction with rabbit platelets. Arch Biochem Biophys. 1983 Jul 15;224(2):485–493. doi: 10.1016/0003-9861(83)90236-9. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. Sánchez-Crespo M., Alonso F., Egido J. Platelet-activating factor in anaphylaxis and phagocytosis. I. Release from human peripheral polymorphonuclears and monocytes during the stimulation by ionophore A23187 and phagocytosis but not from degranulating basophils. Immunology. 1980 Aug;40(4):645–655. [PMC free article] [PubMed] [Google Scholar]
  39. Sánchez-Crespo M., Alonso F., Iñarrea P., Alvarez V., Egido J. Vascular actions of synthetic PAF-acether (a synthetic platelet-activating factor) in the rat: evidence for a platelet independent mechanism. Immunopharmacology. 1982 Apr;4(2):173–185. doi: 10.1016/0162-3109(82)90019-4. [DOI] [PubMed] [Google Scholar]
  40. Sánchez-Crespo M., Iñarrea P., Alvarez V., Alonso F., Egido J., Hernando L. Presence in normal human urine of a hypotensive and platelet-activating phospholipid. Am J Physiol. 1983 Jun;244(6):F706–F711. doi: 10.1152/ajprenal.1983.244.6.F706. [DOI] [PubMed] [Google Scholar]
  41. Terashita Z., Imura Y., Nishikawa K., Sumida S. Is platelet activating factor (PAF) a mediator of endotoxin shock? Eur J Pharmacol. 1985 Feb 26;109(2):257–261. doi: 10.1016/0014-2999(85)90427-3. [DOI] [PubMed] [Google Scholar]
  42. Thomas Y., Denizot Y., Dassa E., Boullet C., Benveniste J. Synthèse du paf-acéther par E. coli K12. C R Acad Sci III. 1986;303(17):699–702. [PubMed] [Google Scholar]
  43. Valone F. H., Coles E., Reinhold V. R., Goetzl E. J. Specific binding of phospholipid platelet-activating factor by human platelets. J Immunol. 1982 Oct;129(4):1637–1641. [PubMed] [Google Scholar]
  44. 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]
  45. Valone F. H. Inhibition of binding of the platelet-activating factor AGEPC to platelets by the AGEPC analog rac-3-(N-n-octadecylcarbamoyloxy)-2-methoxypropyl 2-thiazolioethyl phosphate (CV-3988). Biochem Biophys Res Commun. 1985 Jan 16;126(1):502–508. doi: 10.1016/0006-291x(85)90634-5. [DOI] [PubMed] [Google Scholar]
  46. Valone F. H. Isolation of a platelet membrane protein which binds the platelet-activating factor 1-0-hexadecyl-2-acetyl-SN-glycero-3-phosphorylcholine. Immunology. 1984 May;52(1):169–174. [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. Villamediana L. M., Sanz E., Fernandez-Gallardo S., Caramelo C., Sanchez Crespo M., Braquet P., Lopez-Novoa J. M. Effects of the platelet-activating factor antagonist BN 52021 on the hemodynamics of rats with experimental cirrhosis of the liver. Life Sci. 1986 Jul 21;39(3):201–205. doi: 10.1016/0024-3205(86)90531-x. [DOI] [PubMed] [Google Scholar]
  49. Weinstein M. P., Reller L. B., Murphy J. R., Lichtenstein K. A. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev Infect Dis. 1983 Jan-Feb;5(1):35–53. doi: 10.1093/clinids/5.1.35. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES