Involvement of Platelet-Activating Factor in Neurological Disorders

Platelet-activating factor (PAF) is a potent proinflammatory lipid mediator that is not stored, but synthesized by activated neural cells (neurons, astrocytes, oligodendrocytes, and microglial cells) as well as by nonneural cells (platelets, inflammatory, and endothelial cells) on demand by remodeling and de novo synthesis pathways. PAF receptors (PAF-Rs) are widely distributed in different brain regions and are present on the cell surface as well as in intracellular membrane compartments. In normal brain, levels of PAF are low, but levels of lyso-PAF are quite high. Thus levels of PAF in the hippocampus are higher than in cerebellum and cortex. These observations suggest that PAF is present in its inactive form in the brain tissue (Tiberghien et al., 1991). Concentration of PAF decreases with age (Tokumura et al., 1992). Under normal conditions, the synthesis of PAF in brain occurs through de novo synthesis. Normally, de novo synthesis is not influenced by the external stimulus. In response to PAF-R stimulation, injury, chemoelectroconvulsion and oxidative stress, the remodeling pathway is activated in neural and nonneural cells. Treatment of neural or nonneural cells with neurotransmitters such as dopamine and acetylcholine stimulates PAF synthesis in a calcium-dependent manner (Sogos et al., 1990). PAF is also synthesized by neurons and glial cells following stimulation with glutamate. PAF synthesis requires glutamate-mediated stimulation of NMDA receptors and subsequent elevation of intracellular calcium ions.

Microglia, which express functional PAF-Rs to a high level show a marked chemotactic response to PAF. Microglia derived from PAF-receptor-deficient mice do not show chemotactic response (Aihara et al., 2000). Thus, PAF functions as a key messenger in neuron–microglial interactions. PAF-Rs generate specific signals that are transduced by downstream effector and pathways, which may be specific to each brain cell type. Although the synthesis and release of PAF under pathological conditions in the brain has been recognized, the relative contribution of various neural and nonneural cell types for the synthesis of PAF remains unknown. Furthermore, target cells and brain regions for PAF action have not been fully identified.


Experimental Autoimmune Encephalomyelitis Bacterial Meningitis Platelet Activate Factor Platelet Activate Factor Antagonist Platelet Activate Factor Level 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arditi M., Manogue K. R., Caplan M., and Yogev R. (1990). Cerebrospinal fluid cachectin/tumor necrosis factor-α and platelet-activating factor concentrations and severity of bacterial meningitis in children. J. Infect. Dis. 162:139–147.PubMedGoogle Scholar
  2. Adachi T., Aoki J., Manya H., Asou H., Arai H., and Inoue K. (1997). PAF analogues capable of inhibiting PAF acetylhydrolase activity suppress migration of isolated rat cerebellar granule cells. Neurosci. Lett. 235:133–136.PubMedGoogle Scholar
  3. Adunsky A., Hershkowitz M., Atar E., Bakoun M., and Poreh A. (1999). Infarct volume, neurological severity and PAF binding to platelets of patients with acute cerebral ischemic stroke. Neurol. Res. 21:645–648.PubMedGoogle Scholar
  4. Aihara M., Ishii S., Kume K., and Shimizu T. (2000). Interaction between neurone and microglia mediated by platelet-activating factor. Genes Cells. 5:397–406.PubMedGoogle Scholar
  5. Akisu M., Huseyinov A., Yalaz M., Cetin H., Kultursay N. (2003). Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia. Prostaglandins Leukot. Essent. Fatty Acids. 69:45–50.PubMedGoogle Scholar
  6. Anrather J., Racchumi G., and Iadecola C. (2006). NF-κB regulates phagocytic NADPH oxidase by inducing the expression of gp91phox. J. Biol. Chem. 281:5657–5667.PubMedGoogle Scholar
  7. Arimura A., Nagata M., Watanabe A., Nakamura K., Takeuchi M., and Harada M. (1990). Production of active and passive anaphylactic shock in the WBB6F1 mouse, a mast cell-deficient strain. Experientia. 46:739–742.PubMedGoogle Scholar
  8. Bate C., Salmona M., and Williams A. (2004a). The role of platelet activating factor in prion and amyloid-beta neurotoxicity. NeuroReport. 15:509–513.PubMedGoogle Scholar
  9. Bate C., Reid S., and Williams A. (2004b). Phospholipase A2 inhibitors or platelet-activating factor antagonists prevent prion replication. J. Biol. Chem. 279:36405–36411.PubMedGoogle Scholar
  10. Bate C., Salmona M., Diomede L., and Williams A. (2004c). Squalestatin cures prion-infected neurons and protects against prion neurotoxicity. J. Biol. Chem. 279:14983–14990.PubMedGoogle Scholar
  11. Bate C., Salmona M., and Williams A. (2004d). Ginkgolide B inhibits the neurotoxicity of prions or amyloid-beta1–42. J. Neuroinflamm. 1:4.Google Scholar
  12. Bazan N. G. (1998). The neuromessenger platelet-activating factor in plasticity and neurodegeneration. Prog. Brain Res. 118:281–291.PubMedGoogle Scholar
  13. Bazan N. G., Packard M. G., Teather L., and Allan G. (1997). Bioactive lipids in excitatory neurotransmission and neuronal plasticity. Neurochem. Int. 30:225–231.PubMedGoogle Scholar
  14. Bellizzi M. J., Lu S. M., Masliah E., and Gelbard H. A. (2005). Synaptic activity becomes excitotoxic in neurons exposed to elevated levels of platelet-activating factor. J. Clin. Invest. 115:3185–3192.PubMedGoogle Scholar
  15. Bennett S. A., Chen J., Pappas B. A., Roberts D. C., and Tenniswood M. (1998). Platelet activating factor receptor expression is associated with neuronal apoptosis in an in vivo model of excitotoxicity. Cell Death Differ. 5:867–875.PubMedGoogle Scholar
  16. Birkle D. L., Kurian P., Braquet P., and Bazan N. G. (1988). Platelet-activating factor antagonist BN52021 decreases accumulation of free polyunsaturated fatty acid in mouse brain during ischemia and electroconvulsive shock. J. Neurochem. 51:1900–1905.PubMedGoogle Scholar
  17. Bix G. J., and Clark G. D. (1998). Platelet-activating factor receptor stimulation disrupts neuronal migration in vitro. J. Neurosci. 18:307–318.PubMedGoogle Scholar
  18. Blasquez C., Jegou S., Delarue C., Delbrnde C., Bunel D. T., Blasquez P., and Vaudry H. (1990). Effect of platelet-activating factor on hypothalamic and hypophyseal pro-opiomelanocortin-related peptides and hypothalamo-pituitary-adrenal axis in the rat. Eur. J. Pharmacol. 177:145–153.PubMedGoogle Scholar
  19. Brochet B., Guinot P., Orgogozo J. M., Confavreux C., Rumbach L., Lavergne V., and The Ginkgolide Study Group in Multiple Sclerosis. (1995). Double blind placebo controlled multicentre study of ginkgolide B in treatment of acute exacerbations of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 58:360–362.PubMedGoogle Scholar
  20. Cabellos C., MacIntyre D. E., Forrest M., Burroughs M., Prasad S., and Tuomanen E. (1992). Differing roles for platelet-activating factor during inflammation of the lung and subarachnoid space. The special case of Streptococcus pneumoniae. J. Clin. Invest. 90:612–618.PubMedGoogle Scholar
  21. Callea L., Arese M., Orlandini A., Bargnani C., Priori A., and Bussolino F. (1999). Platelet activating factor is elevated in cerebral spinal fluid and plasma of patients with relapsing-remitting multiple sclerosis. J. Neuroimmunol. 94:212–221.PubMedGoogle Scholar
  22. Camussi G., Tetta C., and Baglioni C. (1990). Antiflammins inhibit synthesis of platelet-activating factor and intradermal inflammatory reactions. Adv. Exp. Med. Biol. 279:161–172.PubMedGoogle Scholar
  23. Catalan R. E., Martinez A. M., Aragones M. D., Fernandez I., Miguel B. G., Calcerrada M. C., and Perez M. J. (1994). Platelet-activating factor inhibits Na+, K+ ATPase activity in rat brain. Neurosci. Res. 19:241–244.PubMedGoogle Scholar
  24. Cederholm A., Svenungsson E., Stengel D., Fei G. Z., Pockley A. G., Ninio E., and Frostegard J. (2004). Platelet-activating factor-acetylhydrolase and other novel risk and protective factors for cardiovascular disease in systemic lupus erythematosus. Arthritis Rheum. 50:2869–2876.PubMedGoogle Scholar
  25. Chang H. W., Kwon S., Kim H., Lee K., Kim M., Moon T., and Baek S. (2002). Platelet-activating factor acetylhydrolase activity in cerebrospinal fluid of children with acute systemic or neurological illness. Ann. Neurol. 51:760–763.PubMedGoogle Scholar
  26. Chao W., and Olson M. S. (1993). Platelet-activating factor: Receptors and signal transduction. Biochem. J. 292:617–629.PubMedGoogle Scholar
  27. Chong S. S., Pack S. D., Roschke A. V., Tanigami A., Carrozzo R., Smith A. C., Dobyns W. B., and Ledbetter D. H. (1997). A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3. Hum. Mol. Genet. 6:147–155.PubMedGoogle Scholar
  28. Clark G. D., Happel L. T., Zorumski C. F., and Bazan N. G. (1992). Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron. 9:1211–1216.PubMedGoogle Scholar
  29. Clark G. D., Zorumski C. F., McNeil R. S., Happel L. T., Ovella T., McGuire S., Bix G. J., and Swann J. W. (2000). Neuronal platelet-activating factor receptor signal transduction involves a pertussis toxin-sensitive G-protein. Neurochem. Res. 25:603–611.PubMedGoogle Scholar
  30. Cundell D. R., Gerard N. P., Gerard C., Idanpaan H. I., and Tuomanen E. I. (1995). Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature. 377:435–438.PubMedGoogle Scholar
  31. De Coster M. A., Mukherjee P. K., Davis R. J., and Bazan N. G. (1998). Platelet-activating factor is a downstream messenger of kainate-induced activation of mitogen-activated protein kinases in primary hippocampal neurons. J. Neurosci. Res. 53:297–303.Google Scholar
  32. Del Sorbo L., DeMartino A., Biancone L., Bussolati B., Conaldi P. G., Tonioli A., and Cammassi G. (1999). The synthesis of platelet-activating factor modulates chemotaxis of monocytes induced by HIV-1 Tat. Eur. J Immunol. 29:1513–1521.PubMedGoogle Scholar
  33. Faden A. I., and Tzendzalian P. A. (1992). Platelet-activating factor antagonists limit glycine changes and behavioral deficits after brain trauma. Am. J. Physiol. 263:R909–R914.PubMedGoogle Scholar
  34. Farooqui A. A., and Horrocks L. A. (2004). Plasmalogens, and other ether lipids. In Ether Lipids, A. Nicolaou and G. Kokotos (Eds.). Oily, Bridgwater, England, pp. 107–134.Google Scholar
  35. Farooqui A. A., Horrocks L. A., and Farooqui T. (2007). Modulation of inflammation in brain: A matter of fat. J. Neurochem. 101:577–599.PubMedGoogle Scholar
  36. Feuerstein G. Z. (1996). Platelet-activating factor: A case for its role in CNS function and brain injury. J. Lipid Mediat. Cell Signal. 14:109–114.PubMedGoogle Scholar
  37. Frey R. S., Gao X., Javaid K., Siddiqui S. S., Rahman A., and Malik A. B. (2006). Phosphatidylinositol 3-kinase ɣ signaling through protein kinase Cζ induces NADPH oxidase-mediated oxidant generation and NF-κB activation in endothelial cells. J. Biol. Chem. 281:16128–16138.PubMedGoogle Scholar
  38. Gelbard H. A., Nottet H. S., Swindell S., Jett M., Dzenko K. A., Genis P., White P., Wang L., Choi Y. B., and Zhang D. (1994). Platelet-activating factor: A candidate human immunodeficiency virus type 1-induced neurotoxin. J. Virol. 68:4628–4635.PubMedGoogle Scholar
  39. Gilboe D. D., Kintner D., Fitzpatrick J. H., Emoto S. E., Esanu A., Braquet P. G., and Bazan N. G. (1991). Recovery of post-ischemic brain metabolism and function following treatment with a free radical scavenger and platelet-activating factor antagonists. J. Neurochem. 56:311–319.PubMedGoogle Scholar
  40. Glass J. D., and Wesselingh S. L. (2001). Microglia in HIV-associated neurological diseases. Microsc. Res. Tech. 54:95–105.PubMedGoogle Scholar
  41. Graham R. M., Strahan M. E., Norman K. W., Watkins D. N., Strum M. J., and Taylor R. R. (1994). Platelet and plasma platelet-activating factor in sepsis and myocardial infarction. J. Lipid Mediat. Cell Signal. 9:167–182.PubMedGoogle Scholar
  42. Grissom C. K., Orme J. F., Jr., Richer L. D., McIntyre T. M., Zimmerman G. A., and Elstad M. R. (2003). Platelet-activating factor acetylhydrolase is increased in lung lavage fluid from patients with acute respiratory distress syndrome. Crit. Care Med. 31:770–775.PubMedGoogle Scholar
  43. Guo Z. M., Qian C., Peters C. J., and Liu C. T. (1993). Changes in platelet-activating factor, catecholamine, and serotonin concentrations in brain, cerebrospinal fluid, and plasma of pichinde virus-infected guinea pigs. Lab. Anim. Sci. 43:569–574.PubMedGoogle Scholar
  44. Hattori M., Adachi H., Tsijimoto M., Arai H., Inoue K. (1994). Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase. Nature. 370:216–218.PubMedGoogle Scholar
  45. Hirashima Y., Kato R., Endo S., Takaku A., Karasawa K., and Nojima S. (1993a). Immunofluorescent localization of platelet-activating factor (PAF) in the rat. Histochem. J. 25:830–833.PubMedGoogle Scholar
  46. Hirashima Y., Endo S., Otsuji T., Karasawa K., Nojima S., and Takaku A. (1993b). Platelet-activating factor and cerebral vasospasm following subarachnoid hemorrhage. J. Neurosurg. 78:592–597.PubMedGoogle Scholar
  47. Hirashima Y., Endo S., Ohmori T., Kato R., and Takaku A. (1994). Platelet-activating factor (PAF) concentration and PAF acetylhydrolase activity in cerebrospinal fluid of patients with subarachnoid hemorrhage. J. Neurosurg. 80:31–36.PubMedGoogle Scholar
  48. Hirashima Y., Endo S., KaraSawa K., Sato N., YokoYama K., Kurimoto M., Ikeda H., Setaka M., and Takaku A. (1999). Deficient platelet-activating factor and related enzymes in hemimegalencephaly. Childs Nerv. Syst. 15:98–101.PubMedGoogle Scholar
  49. Honda Z., Ishii S., and Shimizu T. (2002). Platelet-activating factor receptor. J. Biochem. 131:773–779.PubMedGoogle Scholar
  50. Hostettler M. E., and Carlson S. L. (2002). PAF antagonist treatment reduces pro-inflammatory cytokine mRNA after spinal cord injury. Neuroreport. 13:21–24.PubMedGoogle Scholar
  51. Hostettler M. E., Knapp P. E., and Carlson S. L. (2002). Platelet-activating factor induces cell death in cultured astrocytes and oligodendrocytes: Involvement of caspase-3. Glia. 38:228–239.PubMedGoogle Scholar
  52. Ishii I., Izumi T., Ui M., and Shimizu T. (1997). High and low affinity mutants of platelet-activating factor receptor. Adv. Exp. Med. Biol. 433:249–253.PubMedGoogle Scholar
  53. Ishii S., and Shimizu T. (2000). Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice. Prog. Lipid Res. 39:41–82.PubMedGoogle Scholar
  54. Kald B., Smedh K., Olaison G., Sjodahl R., and Tagesson C. (1996). Platelet-activating factor acetylhydrolase activity in intestinal mucosa and plasma of patients with Crohn’s disease. Digestion. 57:472–477.PubMedGoogle Scholar
  55. Karcher L., Zagermann P., and Krieglstein J. (1984). Effect of an extract of Ginkgo biloba on rat brain energy metabolism in hypoxia. Naunyn Schmiedebergs Arch. Pharmakol. 327:31–35.Google Scholar
  56. Kelley D. S., Taylor P. C., Nelson G. J., Schmidt P. C., Ferretti A., Erickson K. L., Yu R., Chandra R. K., and Mackey B. E. (1999). Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids. 34:317–324.PubMedGoogle Scholar
  57. Kihara Y., Ishii S., Kita Y., Toda A., Shimada A., and Shimizu T. (2005). Dual phase regulation of experimental allergic encephalomyelitis by platelet-activating factor. J. Exp. Med. 202:853–863.PubMedGoogle Scholar
  58. Kim H. J., Lee S. R., and Moon K. D. (2003). Ether fraction of methanol extracts of Gastrodia elata, medicinal herb protects against neuronal cell damage after transient global ischemia in gerbils. Phytother. Res. 17:909–912.PubMedGoogle Scholar
  59. Ko H. M., Seo K. H., Han S. J., Ahn K. Y., Choi I. H., Koh G. Y., Lee H. K., Ra M. S., and Im S. Y. (2002). Nuclear factor kappa B dependency of platelet-activating factor-induced angiogenesis. Cancer Res. 62:1809–1814.PubMedGoogle Scholar
  60. Kravchenko V. V., Pan Z., Han J., Herbert J. M., Ulevitch R. J., and Ye R. D. (1995). Platelet-activating factor induces NF-kappa B activation through a G protein-coupled pathway. J. Biol. Chem. 270:14928–14934.PubMedGoogle Scholar
  61. Kumar R., Harvey S. A., Kester M., Hanahan D. J., and Olson M. S. (1988). Production and effects of platelet-activating factor in the rat brain. Biochim. Biophys. Acta. 963:375–383.PubMedGoogle Scholar
  62. Lindsberg P. J., Hallenbeck J. M., and Feuerstein G. (1991). Platelet-activating factor in stroke and brain injury. Ann. Neurol. 30:117–129.PubMedGoogle Scholar
  63. Maclennan K. M., Smith P. F., and Darlington C. L. (1996). Platelet-activating factor in the CNS. Prog. Neurobiol. 50:585–596.PubMedGoogle Scholar
  64. Makristathis A., Stauffer F., Feistauer S. M., Georgopoulos A. (1993). Bacteria induce release of platelet-activating factor (PAF) from polymorphonuclear neutrophil granulocytes: Possible role for PAF in pathogenesis of experimentally induced bacterial pneumonia. Infect. Immun. 61:1996–2002.PubMedGoogle Scholar
  65. Manya H., Aoki J., Kato H., Ishii J., Hino S., Arai H., and Inoue K. (1999). Biochemical characterization of various catalytic complexes of the brain platelet-activating factor acetylhydrolase. J. Biol. Chem. 274:31827–31832.PubMedGoogle Scholar
  66. Margues S. A., Dy L. C., Southall M. D., Yi O., Smietana E., Kapur R., Margues M., Travers J. B., and Spandau D. F. (2002). The platelet-activating factor receptor activates the extracellular signal-regulated kinase mitogen-activated protein kinase and induces proliferation of epidermal cells through an epidermal growth factor-receptor-dependent pathway. J. Pharmacol. Exp. Ther. 300:1026–1035.Google Scholar
  67. Miller A. A., Drummond G. R., and Sobey C. G. (2006). Novel isoforms of NADPH-oxidase in cerebral vascular control. Pharmacol. Ther. 111:928–948.PubMedGoogle Scholar
  68. Moon T. C., Kim M. S., Lee S. J., Lee T. Y., Kwon S. H., Baek S. H., and Chang H. W. (2003). Detection and characterization of 45 kDa platelet activating factor acetylhydrolase in cerebrospinal fluid of children with meningitis. Arch. Pharm. Res. 26:554–558.PubMedGoogle Scholar
  69. Mueller H. W., Haught C. A., McNatt J. M., Chi K., Gaskell S. J., Johnston D. A., and Willerson J. T. (1995). Measurement of platelet-activating factor in a canine model of coronary thrombosis and in endarterectomy samples from patients with advanced coronary artery disease. Circ. Res. 77:54–63.PubMedGoogle Scholar
  70. Mueller M. H., Geis M., Glatzle J., Kasparek M., Meile T., Jehle E. C., Kreis M. E., and Zittel T. T. (2007). Risk of fecal diversion in complicated perianal Crohn’s disease. J. Gastrointest. Surg. 11:529–537.PubMedGoogle Scholar
  71. Nagase T., Ishii S., Katayama H., Fukuchi Y., Ouchi Y., and Shimizu T. (1997). Airway responsiveness in transgenic mice overexpressing platelet-activating factor receptor. Roles of thromboxanes and leukotrienes. Am. J. Respir. Crit. Care Med. 156:1621–1627.PubMedGoogle Scholar
  72. Nagase T., Kurihara H., Kurihara Y., Aoki-Nagase T., Nagai R., and Ouchi Y. (1999). Disruption of ET-1 gene enhances pulmonary responses to methacholine via functional mechanism in knockout mice. J. Appl. Physiol. 87:2020–2024.PubMedGoogle Scholar
  73. Nishida K., Markey S. P., Kustova Y., Morse H. C., Skolnick P., Basile A. S., and Sei Y. (1996). Increased brain levels of platelet-activating factor in a murine acquired immune deficiency syndrome are NMDA receptor-mediated. J. Neurochem. 66:433–435.PubMedGoogle Scholar
  74. Noris M., Benigni A., Boccardo P., Gotti E., Benfenati E., Aiello S., Todeschini M., and Remmuzzi G. (1993). Urinary excretion of platelet activating factor in patients with immune-mediated glomerulonephritis. Kidney Int. 43:426–429.PubMedGoogle Scholar
  75. Nottet H. S., Jett M., Flanagan C. R., Zhai Q. H., Persidsky Y., Rizzino A., Bernton E. W., Genis P., Baldwin T., Schwartz J. H., LaBenz C. J., and Gendelman H. E. (1995). A regulatory role for astrocytes in HIV-1 encephalitis. An overexpression of eicosanoids, platelet-activating factor, and tumor necrosis factor-alpha by activated HIV-1-infected monocytes is attenuated by primary human astrocytes. J. Immunol. 154:3567–3581.PubMedGoogle Scholar
  76. Partrick D. A., Moore E. E., Moore F. A., Biffl W. L., and Barnett C. C. (1997). Reduced PAF-acetylhydrolase activity is associated with postinjury multiple organ failure. Shock. 7:170–174.PubMedGoogle Scholar
  77. Quarck R., De Geest B., Stengel D., Mertens A., Lox M., Theilmeier G., Michiels C., Raes M., Bult H., Collen D., Van Veldhoven P., Ninio E., and Holvolt P. (2001). Adenovirus-mediated gene transfer of human platelet-activating factor-acetylhydrolase prevents injury-induced neointima formation and reduces spontaneous atherosclerosis in apolipoprotein E-deficient mice. Circulation. 103:2495–2500.PubMedGoogle Scholar
  78. Rehder V., Jensen J. R., and Kater S. B. (1992). The initial stages of neural regeneration are dependent upon intracellular calcium levels. Neuroscience. 51:565–574.PubMedGoogle Scholar
  79. Ring A., Weiser J. N., and Tuomanen E. I. (1998). Pneumococcal trafficking across the blood–brain barrier. Molecular analysis of a novel bidirectional pathway. J. Clin. Invest. 102:347–360.PubMedGoogle Scholar
  80. Rubin B. B., Downey G. P., Koh A., Degousee N., Ghomashchi F., Nallan L., Stefanski E., Harkin D. W., Sun C. X., Smart B. P., Lindsay T. F., Cherepanov V., Vachon E., Kelvin D., Sadilek M., Brown G. E., Yaffe M. B., Plumb J., Grinstein S., Glogauer M., and Gelb M. H. (2005). Cytosolic phospholipase A2–α is necessary for platelet-activating factor biosynthesis, efficient neutrophil-mediated bacterial killing, and the innate immune response to pulmonary infection–cPLA2–α does not regulate neutrophil NADPH oxidase activity. J. Biol. Chem. 280:7519–7529.PubMedGoogle Scholar
  81. Sarchielli P., Alberti A., Coppola F., Baldi A., Gallai B., Floridi A., Floridi A., Capocchi G., and Gallai V. (2004). Platelet-activating factor (PAF) in internal jugular venous blood of migraine without aura patients assessed during migraine attacks. Cephalalgia. 24:623–630.PubMedGoogle Scholar
  82. Schifitto G., Sacktor N., Marder K., McDermott M. P., McArthur J. C., Kieburtz K., Small S., Epstein L. G., and The Neurological AIDS Research Consortium. (1999). Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurology. 53:391–396.PubMedGoogle Scholar
  83. Serebruany V. L., Gurbel P. A., Murugesan S. R., Lowry D. R., Sturm E., and Svetlov S. I. (1998). Depressed plasma platelet-activating factor acetylhydrolase in patients presenting with acute myocardial infarction. Cardiology. 90:127–130.PubMedGoogle Scholar
  84. Serradji N., Martin M., Bensaid O., Cisternino S., Rousselle C., Dereuddre-Bosquet N., Huet J., Redeuilh C., Lamouri A., Doug L. Z., Clayette P., Scherrmann J. M., Dormont D., and Heymans F. (2004). Structure–activity relationships in platelet-activating factor. 12. Synthesis and biological evaluation of platelet-activating factor antagonists with anti-HIV-1 activity. J. Med. Chem. 47:6410–6419.PubMedGoogle Scholar
  85. Shi L. C., Wang H. Y., and Friedman E. (1998). Involvement of platelet-activating factor in cell death induced under ischemia/postischemia-like conditions in an immortalized hippocampal cell line. J. Neurochem. 70:1035–1044.PubMedCrossRefGoogle Scholar
  86. Shmueli O., Cahana A., and Reiner O. (1999). Platelet-activating factor (PAF) acetylhydrolase activity, LIS1 expression, and seizures. J. Neurosci. Res. 57:176–184.PubMedGoogle Scholar
  87. Sogos V., Bussolino F., Pilia E., Torrelli S., and Gremo F. (1990). Acetylcholine-induced production of platelet-activating factor by human fetal brain cells in culture. J. Neurosci. Res. 27:706–711.PubMedGoogle Scholar
  88. Shmelzer Z., Haddad N., Admon E., Pessach I., Leto T. L., Eitan-Hazan Z., Hershfinkel M., and Levy R. (2003). Unique targeting of cytosolic phospholipase A2 to plasma membranes mediated by the NADPH oxidase in phagocytes. J. Cell Biol. 162:683–692.PubMedGoogle Scholar
  89. Tai C. Y., Dujardin D. L., Faulkner N. E., and Vallee R. B. (2002). Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function. J. Cell Biol. 156:959–968.PubMedGoogle Scholar
  90. Takehara S., Mikashima H., Muramoto Y., Terasawa M., Setoguchi M., and Tahara T. (1990). Pharmacological actions of Y-24180, a new specific antagonist of platelet activating factor (PAF). II. Interactions with PAF and benzodiazepine receptors. Prostaglandins. 40:571–583.PubMedGoogle Scholar
  91. Tanaka T., Iimori M., Tsukatani H., Tokumura A. (1994). Platelet-aggregating effects of platelet-activating factor-like phospholipids formed by oxidation of phosphatidylcholines containing an sn-2-polyunsaturated fatty acyl group. Biochim. Biophys. Acta. 1210:202–208.PubMedGoogle Scholar
  92. Tanaka T., Serneo F. F., Higgins C., Gambello M. J., Wynshaw-Boris A., and Gleeson J. G. (2004). Lis1 and doublecortin function with dynein to mediate coupling of the nucleus to the centrosome in neuronal migration. J. Cell Biol. 165:709–721.PubMedGoogle Scholar
  93. Taylor K. E., Richardson A. J., and Stein J. F. (2001). Could platelet activating factor play a role in developmental dyslexia? Prostaglandins Leukot. Essent. Fatty Acids. 64:173–180.Google Scholar
  94. Tetta C., Bussolino F., Modena V., Montrucchio G., Segoloni G., Pescarmona G., and Camussi G. (1990). Release of platelet-activating factor in systemic lupus erythematosus. Int. Arch. Allergy Appl. Immunol. 91:244–256.PubMedGoogle Scholar
  95. Tiberghien C., Laurent L., Junier M. P., and Dray F. (1991). A competitive receptor binding assay for platelet-activating factor (PAF): Quantification of PAF in rat brain. J. Lipid Mediat. 3:249–266.PubMedGoogle Scholar
  96. Tjoelker L. W., and Stafforini D. M. (2000). Platelet-activating factor acetylhydrolases in health and disease. Biochim. Biophys. Acta. 1488:102–123.PubMedGoogle Scholar
  97. Tokumura A., Tsutsumi T., and Tsukatani H. (1992). Transbilayer movement and metabolic fate of ether-linked phosphatidic acid (1-O-octadecyl-2-acetyl-sn-glycerol 3-phosphate) in guinea pig peritoneal polymorphonuclear leukocytes. J. Biol. Chem. 267:7275–7283.PubMedGoogle Scholar
  98. Tokutomi T., Maruiwa H., Hirohata M., Miyagi T., and Shigemori M. (2001). Production of platelet-activating factor by neuronal cells in the rat brain with cold injury. Neurol. Res. 23:605–611.PubMedGoogle Scholar
  99. Tselepis A. D., Elisaf M., Besis S., Karabina S. A., Chapman M. J., and Siamopoulou A. (1999). Association of the inflammatory state in active juvenile rheumatoid arthritis with hypo-high-density lipoproteinemia and reduced lipoprotein-associated platelet-activating factor acetylhydrolase activity. Arthritis Rheum. 42:373–383.PubMedGoogle Scholar
  100. Tsukioka K., Matsuzaki M., Nakamata M., Kayahara H., and Nakagawa T. (1996). Increased plasma level of platelet-activating factor (PAF) and decreased serum PAF acetylhydrolase (PAFAH) activity in adults with bronchial asthma. J. Invest. Allergol. Clin. Immunol. 6:22–29.Google Scholar
  101. Turunen P., Puhakka H., Rutanen J., Hiltunen M. O., Heikura T., Gruchala M., Yla-Herttuala S. (2005). Intravascular adenovirus-mediated lipoprotein-associated phospholipase A2 gene transfer reduces neointima formation in balloon-denuded rabbit aorta. Atherosclerosis. 179:27–33.PubMedGoogle Scholar
  102. Unno N., Nakamura T., Kaneko H., Uchiyama T., Yamamoto N., Sugatani J., Miwa M., and Nakamura S. (2000). Plasma platelet-activating factor acetylhydrolase deficiency is associated with atherosclerotic occlusive disease in Japan. J. Vasc. Surg. 32:263–267.PubMedGoogle Scholar
  103. Yamada Y., Yoshida H., Ichihara S., Imaizumi T., Satoh K., and Yotaka M. (2000). Correlations between plasma platelet-activating factor acetylhydrolase (PAF-AH) activity and PAF-AH genotype, age, and atherosclerosis in a Japanese population. Atherosclerosis. 150:209–216.PubMedGoogle Scholar
  104. Yamamoto Y., and Gaynor R. B. (2004). IkappaB kinases: Key regulators of the NF-kappa B pathway. Trends Biochem. Sci. 29:72–79.PubMedGoogle Scholar
  105. Zablocka B., Lukasiuk K., Lazarewicz J. W., and Domanska-Janik S. (1995). Modulation of ischemic signal by antagonists of N-methyl-D-aspartate, nitric oxide synthase, and platelet-activating factor in gerbil hippocampus. J. Neurosci. Res. 40:233–240.PubMedGoogle Scholar
  106. Zhang X., Pan X. L., Liu X. T., Wang S., and Wang L. J. (2007). Down-regulation of platelet-activating factor receptor gene expression during focal reversible cerebral ischemia in rats. Neurochem. Res. 32:451–456.PubMedGoogle Scholar
  107. Zhu J., Brackett N. L., Aballa T. C., Lynne C. M., Witt M. A., Kort H. I., and Roudebush W. E. (2006). High seminal platelet-activating factor acetylhydrolase activity in men with spinal cord injury. J. Androl. 27:429–433.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Personalised recommendations