Platelet-Activating Factor in the CNS

Maclennan, Karyn; Smith, Paul F.; Darlington, Cynthia L.

doi:10.1016/s0301-0082(96)00047-0

Cited by 78 publications

(45 citation statements)

References 98 publications

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“…Moreover, we now know that these unique phospholipids may participate in diverse (patho)physiologic events, including cell-cell adhesive interactions, intra-and intercellular signal transduction, cell differentiation, apoptosis, angiogenesis, neurotransmission, reproductive biology, cardiovascular homeostasis, ocular physiology, allergy, gastrointestinal, renal, or pulmonary tissue injury, organ transplantation rejection, and septic shock or systemic inflammatory response syndrome (cf. Zimmerman et al, 1993Zimmerman et al, , 1997Tokumura, 1995;Izzo, 1996;Maclennan et al, 1996;Bazan et al, 1997;Feuerstein et al, 1997;Muzya, 1997, 1998;Mathiak et al, 1997;Muguruma et al, 1997;Prescott, 1997;Tetta et al, 1997;Fink, 1998;Bazan, 1998 chronic inflammation. These inflammatory cells include the PMN, monocyte/macrophage, vascular endothelial cell, lymphocyte, mast cell, basophil, eosinophil, and platelet.…”

Section: (I) Introductionmentioning

confidence: 99%

“…Details regarding much of this PAF pathobiology are provided in a series of relatively recent reviews (cf. Zimmerman et al, 1993Zimmerman et al, , 1997Tokumura, 1995;Izo, 1996;Maclennan et al, 1996;Bazan et at., 1997;Feuerstein et al, 1997;Muzya, 1997, 1998;Mathiak et at, 1997;Muguruma et at., 1997;Prescott, 1997;Tetta et at., 1997;Fink, 1998;Kulikov and Muzya, 1998). The following will briefly focus upon the pro-inflammatory properties of PAY.…”

Section: (I) Introductionmentioning

confidence: 99%

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PAF, a Putative Mediator of Oral Inflammation

McManus

Pinckard

2000

Critical Reviews in Oral Biology & Medicine

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PAF, or platelet-activating factor, is a family of structurally related phospholipids (1 -O-alkyl/acyl/alkenyl-2-acetylsn-glycero-3-phosphocholine) which possesses a wide spectrum of potent pro-inflammatory actions. These phospholipids are synthesized by a diverse array of cells, including neutrophilic polymorphonuclear leukocytes (PMN), platelets, mast cells, monocytes/macrophages, vascular endothelial cells, and lymphocytes. PAF targets these and other cells via specific, G-proteincoupled receptors to initiate intracrine, autocrine, paracrine, and juxtacrine cell activation. Of importance, these unique acetylated phospholipids are frequently synthesized in concert with pro-inflammatory lipid mediators derived from arachidonic acid. Since PAF synergizes with these and other mediators to amplify the inflammatory response, it seems likely that PAF plays an integral, perhaps pivotal, role in acute and chronic inflammatory processes. PAF is present in the mixed saliva of dentate, but not edentulous, human subjects. The levels of PAF in mixed saliva or in gingival crevicular fluid and tissues are significantly increased during oral inflammatory conditions such as periodontitis and mucositis. Interestingly, the levels of salivary PAF correlate with the extent/severity of these oral diseases. These observations suggest that PAF may participate in pathophysiologic events during the course of oral inflammation. The availability of specific PAF receptor antagonists and human recombinant PAF-acetylhydrolase (PAF-AH), a plasma enzyme which rapidly destroys PAF, should provide clinical tools for the investigation of the role of PAF in these and other inflammatory disorders; and perhaps, ultimately, some of these reagents may prove to be therapeutically useful in the treatment and management of these conditions.

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Section: (I) Introductionmentioning

confidence: 99%

Section: (I) Introductionmentioning

confidence: 99%

PAF, a Putative Mediator of Oral Inflammation

McManus

Pinckard

2000

Critical Reviews in Oral Biology & Medicine

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“…3 PAF is produced not only by basophils but also by a variety of cells, including neuronal cells. 4 The role of PAF in ischemic injury in the central nervous system (CNS) has been initially proposed based on the results showing that selective PAF receptor antagonists prevented ischemia-induced CNS damage in animal models. 5 Until now, many researchers have reported that PAF contributes to the aggravation of neuronal damage in the postischemic brain as well as in the posttraumatic brain.…”

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confidence: 99%

Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia

Umemura

Kato

Hirashima

et al. 2007

Stroke

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Background and Purpose-Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative stress. We examined whether PAF-AH II can rescue cerebral neurons against ischemic insults. Methods-Transgenic mice overexpressing human PAF-AH II in neurons were generated and enzyme expressions were examined biochemically and histochemically. The mice were subjected to 60 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarction and apoptosis were estimated by TTC staining and fluorescence TUNEL staining, respectively. Results-Overexpression of PAF-AH II was found in brains of transgenic mice by Western blot and enzymatic activity analyses. In immunohistochemistry, human PAF-AH II expression was found throughout the central nervous system, especially in neurons of neocortex, hippocampus, and basal ganglia. The neurological deficit scores, cerebral edema index, and relative infarction volume were all significantly (PϽ0.05) lower in transgenic mice (1.30Ϯ0.72, 1.12Ϯ0.04, and 14.0Ϯ7.7%, respectively) than in wild-type mice (2.56Ϯ0.93, 1.23Ϯ0.12, and 31.9Ϯ9.7%, respectively). Percentages of apoptotic cells were also significantly (PϽ0.001) lower in transgenic mice (cortex, 5.2Ϯ3.3%; hippocampus, 3.4Ϯ7.0%) than in wild-type mice (cortex, 41.1Ϯ16.9%; hippocampus, 58.9Ϯ15.3%). Conclusions-These results indicate that PAF-AH II exerts strong neuroprotective effects against ischemic injury and suggest a possibility for clinical use of this enzyme in cerebral ischemia.

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“…In addition, PAF has been implicated in the central nervous system (2,3) and the reproductive system (4,5). PAF is hydrolyzed to an inactive metabolite by a specific enzyme called PAF-acetylhydrolase (PAF-AH).…”

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confidence: 99%

Targeted Disruption of Intracellular Type I Platelet Activating Factor-acetylhydrolase Catalytic Subunits Causes Severe Impairment in Spermatogenesis

Koizumi

Yamaguchi

Hattori

et al. 2003

Journal of Biological Chemistry

117

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Intracellular type I platelet activating factor-acetylhydrolase is a phospholipase that consists of a dimer of two homologous catalytic subunits ␣1 and ␣2 as well as LIS1, a product of the causative gene for type I lissencephaly. LIS1 plays an important role in neuronal migration during brain development, but the in vivo function of the catalytic subunits remains unclear. In this study, we generated ␣1-and a2-deficient mice by targeted disruption. ␣1 ؊/؊ mice are indistinguishable from wild-type mice, whereas ␣2 ؊/؊ male mice show a significant reduction in testis size. Double-mutant male mice are sterile because of severe impairment of spermatogenesis. Histological examination revealed marked degeneration at the spermatocyte stage and an increase of apoptotic cells in the seminiferous tubules. The catalytic subunits are expressed at high levels in testis as well as brain in mice. In wild-type mice, ␣2 is expressed in all seminiferous tubule cell types, whereas ␣1 is expressed only in the spermatogonia. This expression pattern parallels the finding that deletion of both subunits induces a marked loss of germ cells at an early spermatogenic stage. We also found that the LIS1 protein levels, but not the mRNA levels, were significantly reduced in ␣2 ؊/؊ and double-mutant mice, suggesting that the catalytic subunits, especially ␣2, are a determinant of LIS1 expression level.

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Platelet-Activating Factor in the CNS

Cited by 78 publications

References 98 publications

PAF, a Putative Mediator of Oral Inflammation

PAF, a Putative Mediator of Oral Inflammation

Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia

Targeted Disruption of Intracellular Type I Platelet Activating Factor-acetylhydrolase Catalytic Subunits Causes Severe Impairment in Spermatogenesis

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