Summary
Platelet activating factor (PAF) is a unique phosphoglyceride which possesses many potent biological activities relevant for the pathogenesis of diseases of the elderly. PAF is generated and released by numerous cell types and tissues and is rapidly metabolised through a well defined metabolic cycle. Its biological actions are mediated via direct and indirect stimulatory effects on target cells and tissues. The current knowledge of PAF and its role in cardiovascular disease, thromboembolism, cerebral ischaemia and neurodegenerative disorders are discussed in detail. It is likely, that in future, a better understanding of the pathophysiological and physiological roles of PAF will provide new strategies for the treatment of human diseases of aging.
Similar content being viewed by others
References
Adamus WS, Heuer HO, Meade CJ, Schilling JC. Inhibitory effects of the new PAF acether antagonist WEB 2086 on pharmacologic changes induced by PAF inhalation in human beings. Clinical Pharmacology and Therapeutics 47: 456–462, 1990
Archer CB, Page CP, Paul W, Morley J, McDonald DM. Inflammatory characteristics of platelet activating factor (PAF-acether) in human skin. British Journal of Pharmacology 110: 45–52, 1984
Barbaro JF, Zvaifler NJ. Antigen induced histamine release from platelets and rabbit producing PCA antibody. Proceedings. Society for Experimental Medicine 122: 1245–1247, 1966
Barnes PJ, Chung KF, Page CP. Platelet activating factor as a mediator of allergic disease. Journal of Allergy and Clinical Immunology 81: 919–934, 1989
Benveniste J, Boullet C, Brink C, Labat C. The action of PAF acether (platelet activating factor) on guinea pig isolated heart preparations. British Journal of Pharmacology 80: 81–83, 1983
Benveniste J, Chignard M. A role for PAF-acether (platelet activating factor) in platelet-dependent vascular disease. Circulation 72: 713–717, 1985
Benveniste J, Henson PM, Cochrane CG. Leucocyte dependent histamine release from rabbit platelets: the role of IgE, basophils, and a platelet activating factor. Journal of Experimental Medicine 136: 1356–1377, 1972
Benveniste J, Tence M, Varenne P, Bidault J, Boullet C, et al. Semisynthesis et structure proposee du facteur activant les plaquettes (PAF): PAF-acether, un alkyl ether analoque de la lysophosphatidylcholine. Comptes Rendus. Academie des Seances 289: 1037–1040, 1979
Birkle DL, Kurian P, Braquet P, Bazan NG. Platelet-activating factor antagonist BN 52021 decreases accumulation of free polyunsaturated fatty acid in mouse brain during ischemia and electroconvulsive shock. Journal of Neurochemistry 51: 1900–1905, 1988
Blank ML, Snyder F, Byers LW, Brooks B. Antihypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochemical and Biophysical Research Communications 90: 1194–1200, 1979
Blank ML, Snyder F, Byers WL, Brooks B, Muirhead EE. Antihypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochemical and Biophysical Research Communications 90: 523–534, 1979
Bjork J, Smedegard G. Acute microvascular effects of PAF-acether as studied by intravital microscopy. European Journal of Pharmacology 96: 87–93, 1985
Bourgain R, Maes L, Braquet P, Andries R, Touqui L, et al. The effect of 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF-acether) on the arterial wall. Prostaglandins 30: 185–197, 1985
Bourgain R, Vermarien H, Andries R, Touqui L, Braquet M. A standardized ‘in vivo’ model for the study of experimental arterial thrombosis. Description of the method. Advances in Experimental Medicine and Biology 180: 653–649, 1984
Braquet P, Shen TY, Touqui L, Vargaftig BB. Perspectives in platelet activating factor research/Pharmacological Reviews 39: 97–145, 1987
Brock TA, Gimbrone MA. Platelet activating factor alters calcium hemostasis in cultured endothelial cells. American Journal of Physiology 250: 1086–1092, 1986
Bruynzell PLB, Koenderman PTM, Kok ML, Hameling ML, Verhagen J. Platelet activating factor induces leukotriene C4 formation and luminol dependent chemoluminescence by human eosinophils. Pharmacological Research Communications 18: 61–67, 1986
Burhop RE, van der Zee, Bisios R. Pulmonary vascular responses to platelet activating factor in awake sheep and the role of cyclooxygenase metabolites. American Review of Respiratory Diseases 134: 584–554, 1986
Clerk De F, Gorp LV, Xhonneux B, Sommers Y, Wouters L. Enhanced platelet turnover and prostaglandin production in spontaneously hypertensive rats. Thrombosis Research 27: 243–249, 1982
Demopoulos CA, Pinckard RN, Hanahan DJ. Platelet activating factor: evidence for 1-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active compound (a new class of lipid mediators). Journal of Biological Chemistry 254: 9355–9358, 1979
Dent G, Ukena D, Barnes PJ. PAF receptors. In Barnes et al. (Eds) Platelet activating factor and human disease, pp. 58–81, Blackwell Scientific Publications, Oxford, 1989
D’Humieres S, Russo-Marie F, Vargaftig BB. PAF-acether-induced synthesis of prostaglandin by human endothelial cells. European Journal of Pharmacology 131: 13–19, 1986
Dykens JA, Stern A, Trenkner E. Mechanism of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury. Journal of Neurochemistry 49: 1222–1228, 1987
Ezra D, Laurindo FRM, Czaja JF, Snyder F, Goldstein RE, et al. Cardiac and coronary consequences of intracoronary platelet activating factor infusion in the domestic pig. Prostaglandins 34: 41–57, 1987
Fasules J, Stenmark KR, Henson PM, Voelkel NE, Tucker A, Reves J. Platelet activating factor in lung lavage of chronically hypoxic neonatal calves. American Review of Respiratory Disease 133: A277, 1986
Feuerstein G, Boyd LH, Azra D, Goldstein RE. Effect of platelet activating factor on coronary circulation of the domestic pig. American Journal of Physiology 246: 466–471, 1984
Feuerstein G, Lux WE, Ezra D, Hayes EC, Snyder F, et al. Thyrotropin releasing hormone blocks the hypotensive effect of platelet activating factor in the unanesthetized guinea pig. Journal of Cardiovascular Pharmacology 7: 335–340, 1985
Feuerstein G, Zukowska-Grojec L, Krausz M, Blank ML, Snyder F, et al. Cardiovascular and sympathetic effects of l-O-hexadecyl2-acetyl-sn-glycero-3-phosphorylcholine in conscious SHR and WKY rats. Clinical and Experimental Hypertension 4: 1335–1350, 1982
Fuxe K, Roberts P, Schwarcz R. Excitotoxins, Macmillan, London, 1983
Giembycz M, Kroegel C, Barnes PJ. Platelet activating factor stimulates cyclo-oxygenase activity in guinea pig eosinophils. Concerted biosynthesis of thromboxane A2 and E-series prostaglandins. Journal of Immunology 144: 157–158, 1990
Guinot P, Summerhayes C, Berad L, Duchier J, Revillaud RJ. Treatment of adult systemic mastocytsis with a PAF-acether antagonist BN 52063. Lancet 2: 114, 1988
Handley DA, Lee ML, Saunders RN. Evidence for a direct effect on vascular permeability of platelet activating factor induced hemoconcentration in the guinea pig. Thrombosis and Hemostasis 54: 756–759, 1985
Hartung HP. Acetyl glyceryl ether phosphorylcholine (platelet activating factor) mediates heightened metabolic activity in macrophages. Febs Letters 160: 209–212, 1983
Hayes JP, Ridge SM, Griffith S, Barnes PJ, Chung KF. Inhibition of cutaneous and platelet responses to platelet activating factor by oral WEB 2086 in man. Journal of Allergy and Clinical Immunology 88: 83–88, 1991
Henson PM. Release of vasoactive amines from rabbit platelets induced by sensitized mononuclear leucocytes and antigen. Journal of Experimental Medicine 131: 287–306, 1970
Hosford D, Page CP, Barnes PJ, Braquet P. PAF-receptor antagonists. In Barnes PJ, et al. (Eds) Platelet activating factor in human disease, pp. 82–116, Blackwell Scientific Publications, Oxford, London, Edinburgh, 1989
Humphrey DM, McManus LM, Hanahan DJ, Pinckard RN. Morphological basis of increased vascular permeability induced by acetyl-glyceryl ether phosphorylcholine. Laboratory Investigation 50: 16–25, 1984
Inarrea P, Gomez-Cambronero J, Pascual J, Carmen Ponte M, delHernando L, et al. Synthesis of PAF-acether and blood volume changes in Gram-negative sepsis. Immunopharmacology 9: 4552, 1985
Jackson CV, Schumacher WA, Kunkel SL, Drisoll EM, Pope TK, et al. Platelet activating factor release of platelet-derived coronary artery vasodilator substance in the canine. Circulation Research 58: 218–229, 1986
Jenner P. Neurotoxins and their pharmacological implications, Raven Press, New York, 1987
Kochanek PM, Dutka AJ, Kumaroo KK, Hallenbeck JM. Platelet activating factor receptor blockade enhances neuronal recovery after multi-focal brain ischemia in dogs. Life Sciences 41: 2639–2644, 1987
Kochanek PM, Nemoto EM, Melick JA, Evans RW, Burke DF. Cerebrovascular and cerebrometabolic effects of intracarotid infused platelet activating factor in rats. Journal of Cerebral Blood Flow and Metabolism 8: 546–551, 1988
Koltai M, Hosford D, Guinot P, Esanu A, Braquet P. Platelet activating factor (PAF): a review of its effects, antagonists and possible future clinical implications (Part I). Drugs 42: 9–29, 1991a
Koltai M, Hosford D, Guinot P, Esanu A, Braquet P. PAF: A review of its effects, antagonists and possible future clinical implications (Part II). Drugs 42: 174–204, 1991b
Kornecki E, Ehrlich YH. Neuroregulatory and neuropathological actions of the ether-phospholipid platelet activating factor. Science 240: 1792–1794, 1988
Kroegel C. The potential pathophysiological role of the platelet activating factor (PAF) in human disease. Klinische Wochenschrift 66: 373–378, 1988
Kroegel C. Molecular mechanisms of stimulus-response coupling in human and guinea pig eosinophils. Transduction pathways utilized by platelet activating factor and their relationship to cellular effector functions. PhD Thesis, University of London, 1991a
Kroegel C, Chilvers ER, Giembycz MA, Challis RAJ, Barnes PJ. Platelet activating factor stimulates a rapid accumulation of inositol(1,4,5)trisphosphate in guinea pig eosinophils: relationship to calcium mobilization and degranulation. Journal of Allergy and Clinical Immunology 88: 114–124, 1991b
Kroegel C, Hubbard WH, Lichtenstein LM. Spectrum of prostanoid generation by human blood eosinophils stimulated with platelet activating factor and calcymicin. European Journal of Respiratory Disease 3: 347, 1990
Kroegel C, Yukawa T, Dent G, Venge P, Chung KF, et al. Stimulation of degranulation from human eosinophils by platelet activating factor. Journal of Immunology 142: 3518–3526, 1989
Lai FM, Sheperd CA, Cervoni P, Wissner A. Hypotensive and vasodilatory activity of (+)-1-0-octadecyl-2-acetyl-glyceryl-3phosphorylcholine in the normotensive rat. Life Sciences 32: 1159–1166, 1983
Lepran I, Lefer AM, Ischemia aggravating effects of platelet activating factor in acute myocardial ischemia. Basic Research in Cardiology 80: 135–141, 1985
Lindsberg P, Jacobs TP, Paakari IA, Hallenberg JM, Feuerstein G. Effect of PAF-acether on spinal cord microcirculation. FASEB Journal 2: 455, 1988
MacDermott AB, Mayer ML, Westbrook GL, Smith JL, NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurons. Nature 324: 519–522, 1986
McCormack DM, Barnes PJ, Evans TW, Evidence for platelet activating factor as a mediator of hypoxic pulmonary vasoconstriction. Clinical Science 75: 21, 1988
McManus LM, Hanahan DJ, Demopoulos CA, Pinckard RN. Pathobiology of intravenous infusion of acetylglyceryletherphosphorylcholine (AGEPC), a synthetic platelet activating factor (PAF) in the rabbit. Journal of Immunology 124: 2919–2924, 1980
McMurtry IF, Morris KG. Platelet activating factor causes pulmonary vasodilatation in the rat. American Review of Respiratory Diseases 134: 757–762, 1986
Mehta J, Wargovich T, Nichols WW. Biphasic effects of platelet activating factor on coronary blood flow in the anesthetized dog. Prostaglandins Leukotrienes Medicine 21: 87–95, 1986
Mickelson JK, Simpson PJ, Lucchesi BR. Myocardial dysfunction and coronary vasoconstriction induced by platelet activating factor in post-infarcted isolated heart. Journal of Molecular and Cellular Cardiology 20, 547–561, 1988
Nakaya H, Tohse N. Electrophysiological effects of acethylglyceryletherphosphocholine on cardiac tissue. Comparison with lysophosphatidylcholine and long chain acyl carnitine. British Journal of Pharmacology 89: 749–757, 1986
Panetta T, Marcheselli V, Braquet P, Spinnewyn B, Bazan NG. Effects of a platelet activating factor antagonist (BN 52021) on free fatty acids, diacylglycerols, polyphosphoinositides and blood flow in gerbil brain: inhibition of ischemia-reperfusion induced cerebral injury. Biochemical and Biophysical Research Communications 149: 580–587, 1987
Piper P, Stewart AG. Coronary vasoconstriction in the rat isolated perfused heart induced by platelet activating factor is mediated by leukotriene C4. British Journal of Pharmacology 81: 595–605, 1986
Piper P, Stewart AG. Antagonism of vasoconstriction induced by platelet activating factor in guinea pig perfused hearts by a selective platelet activating factor receptor antagonist. British Journal of Pharmacology 90: 771–783, 1987
Prevost MV, Cariven C, Simon MF, Chap H, Douste-Blazy L. Platelet activating factor (PAF-acether) is released into rat pulmonary alveolar fluid as a consequence of hypoxia. Biochemical and Biophysical Research Communications 119: 58–63, 1984
Roberts NM, Page CP, Chung KF, Barnes PJ. Effect of a PAF antagonist, BN 52063, on antigen induced, acute and late onset cutaneous responses in atopic subjects. Journal of Allergy and Clinical Immunology 136: 623–627, 1989
Robertson DA, Genovese A, Levi R. Negative inotrope effect of platelet activating factor on human myocardium: a pharmacological study. Journal of Pharmacology and Experimental Therapeutics 243: 834–839, 1987
Robertson DA, Wang DY, Lee COK, Levi R. Negative inotrope effect of platelet activating factor: association with a decrease in intracellular sodium activity. Journal of Pharmacology and Experimental Therapeutics 245: 124–128, 1988
Siraganian RP, Osier A. Destruction of rabbit platelets in the allergic response of sensitized leucocytes: demonstration of a fluid phase intermediate. Journal of Immunology 106: 1244–1251, 1971
Siren AL, Feuerstein G. Effects of platelet activating factor and its antagonist, BN 52021, on cardiac function and regional blood flow in the conscious rat. American Journal of Physiology, in press, 1992
Soling HD, Eibl H, Fest W. Acetylcholine-like effects of 1-0-alkyl2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) and its analogues in exocrine secretory glands. European Journal of Biochemistry 144: 65–72, 1984
Spinnewyn B, Blavet N, Clostre F, Bazan N, Braquet P. Involvement of platelet activating factor (PAF) in cerebral post-ischemic phase in Mongolian gerbils. Prostaglandins 34: 337–346, 1987
Tamargo J, Tejerina T, Delgado C, Barrigon S. Electrophysiological effects of platelet activating factor (PAF-acether) in guinea pig papillary muscle. European Journal of Pharmacology 109: 219–227, 1985
Vargaftig BB, Lefort J, Chirgnard M, Benveniste J. Platelet activating factor induces a platelet dependent bronchoconstriction unrelated to the formation of prostaglandin derivates. European Journal of Pharmacology 65: 185–192, 1980
Voelkel N, Worthen S, Reeves J, Henson P, Murphy R. Nonimmunologic production of leukotrienes induced by platelet activating factor. Science 218: 286–288, 1985
Wardlaw AJ, Moqbel R, Cromwell O, Kay AB. Platelet activating factor: a potent chemotactic and chemokinetic factor for human eosinophils. Journal of Clinical Investigation 78: 1701–1706, 1986
Wilkens JH, Wilkens H, Uffmann J, Bovers J, Fabel H, et al. Effects of a specific PAF-antagonist (BN 52063) on bronchoconstriction and platelet activation during exercise induced asthma. British Journal of Clinical Pharmacology 29: 85–91, 1990
Zimmerman GA, McIntyre TM, Prescott SM. Production of platelet activating factor by human vascular endothelial cells: evidence for a requirement for specific agonists and modulation by prostacyclin. Circulation 72: 718–727, 1985
Zukowska-Grojec Z, Blank ML, Snyder F, Feuerstein G. The adrenergic system and the cardiovascular effects of platelet activating factor (1-0-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine) in SHR and WKY rats. Clinical and Experimental Hypertension 7: 1015–1031, 1985
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kroegel, C., Kortsik, C., Kroegel, N. et al. The Pathophysiological Role and Therapeutic Implications of Platelet Activating Factor in Diseases of Aging. Drugs & Aging 2, 345–355 (1992). https://doi.org/10.2165/00002512-199202040-00007
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002512-199202040-00007