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Platelet-activating Factor (Platelet-activat + factor)
Selected AbstractsThe Role of Platelet-activating Factor in the Mammalian Female Reproductive TractREPRODUCTION IN DOMESTIC ANIMALS, Issue 6 2008U Tiemann Contents Platelet-activating factor (PAF) is a potent lipid mediator produced by various cell types of mammals and is involved in an inflammatory-like process with increased vascular permeability. Platelet-activating factor exerts its actions through the activation of specific PAF receptors (PAF-R) found in cells and tissues of the female reproductive tract. The aim of this article was summarized briefly in the current research on the role of PAF in female reproductive functions. Platelet-activating factor has been implicated in processes of ovulation, implantation and parturition because of its angiogenic and growth factor properties. This factor is influenced by ovarian steroid hormones in bringing about changes in the uterus and is a candidate molecule for initial embryo,maternal dialogue. Tissue concentrations of PAF are regulated by the equilibrium between biosynthesis and degradation by PAF-acetylhydrolase (PAF-AH). Antagonists of PAF interfere with ovulation and implantation. Platelet-activating factor, its receptor, and PAF-AH activity play an important role in the maintenance of pregnancy. [source] Post-ischaemic activation of kinases in the pre-conditioning-like cardioprotective effect of the platelet-activating factorACTA PHYSIOLOGICA, Issue 3 2009C. Penna Abstract Aim:, Platelet-activating factor (PAF) triggers cardiac pre-conditioning against ischemia/reperfusion injury. The actual protection of ischaemic pre-conditioning occurs in the reperfusion phase. Therefore, we studied in this phase the kinases involved in PAF-induced pre-conditioning. Methods:, Langendorff-perfused rat hearts underwent 30 min of ischaemia and 2 h of reperfusion (group 1, control). Before ischaemia, group 2 hearts were perfused for 19 min with PAF (2 × 10,11 m); groups 3,5 hearts were co-infused during the initial 20 min of reperfusion, with the protein kinase C (PKC) inhibitor chelerythrine (5 × 10,6 m) or the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (5 × 10,5 m) and atractyloside (2 × 10,5 m), a mitochondrial permeability transition pore (mPTP) opener respectively. Phosphorylation of PKC,, PKB/A,t, GSK-3, and ERK1/2 at the beginning of reperfusion was also checked. Left ventricular pressure and infarct size were determined. Results:, PAF pre-treatment reduced infarct size (33 ± 4% vs. 64 ± 5% of the area at risk of control hearts) and improved pressure recovery. PAF pre-treatment enhanced the phosphorylation/activation of PKC,, PKB/A,t and the phosphorylation/inactivation of GSK-3, at reperfusion. Effects on ERK1/2 phosphorylation were not consistent. Infarct-sparing effect and post-ischaemic functional improvement induced by PAF pre-treatment were abolished by post-ischaemic infusion of either chelerythrine, LY294002 or atractyloside. Conclusions:, The cardioprotective effect exerted by PAF pre-treatment involves activation of PKC and PI3K in post-ischaemic phases and might be mediated by the prevention of mPTP opening in reperfusion via GSK-3, inactivation. [source] Differential platelet-activating factor synthesis by monocytes and polymorphonuclear leukocytes from subjects with localized aggressive periodontitisJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2007C. R. Shin Background and Objective:, Platelet-activating factor is elevated in localized aggressive periodontitis. We previously demonstrated that the elevated level of platelet-activating factor in localized aggressive periodontitis is at least partially attributable to low levels of platelet-activating factor acetylhydrolase, the enzyme that catabolizes platelet-activating factor. The objective of this study was to determine if platelet-activating factor synthesis was also elevated in localized aggressive periodontitis. To test this, platelet-activating factor synthesis was quantified in the monocytes and polymorphonuclear neutrophils of periodontally healthy patients and of subjects with localized aggressive periodontitis. Material and Methods:, Cells were labeled with [3H]acetate and treated with vehicle or stimulated with calcium ionophore A23187. Platelet-activating factor was extracted and quantified by scintillation counting. Results:, For both subject groups, resting monocytes and polymorphonuclear neutrophils produced platelet-activating factor, and calcium ionophore A23187 stimulated platelet-activating factor production in both cell types. However, calcium ionophore A23187-activated monocytes from subjects with localized aggressive periodontitis produced less platelet-activating factor than did activated periodontally healthy monocytes (p < 0.0001), suggesting an aberrant calcium ionophore A23187 response in monocytes from subjects with localized aggressive periodontitis. Indeed, when the data were expressed as fold induction of platelet-activating factor synthesis in response to calcium ionophore A23187, monocytes from subjects with localized aggressive periodontitis exhibited only a fourfold increase in platelet-activating factor synthesis, whereas calcium ionophore A23187-stimulated monocytes from periodontally healthy, chronic periodontitis and generalized aggressive periodontitis subjects produced ,,12 times more platelet-activating factor than did resting monocytes. In contrast, both resting and activated localized aggressive periodontitis polymorphonuclear neutrophils synthesized more platelet-activating factor than did periodontally healthy polymorphonuclear neutrophils. Conclusion:, These data suggest that high levels of platelet-activating factor in subjects with localized aggressive periodontitis result from both increased synthesis and reduced catabolism. While localized aggressive periodontitis polymorphonuclear neutrophils contribute to increased platelet-activating factor mass through synthesis, the contribution of monocytes is probably the result of reduced catabolism by platelet-activating factor acetylhydrolase. [source] Candidate's Thesis: Platelet-Activating Factor,Induced Hearing Loss: Mediated by Nitric Oxide?,THE LARYNGOSCOPE, Issue 12 2003Chung-Ku Rhee MD Abstract Objectives/Hypothesis Platelet-activating factor (PAF)in middle ear effusion is thought to induce hearing loss. The purpose of this study is to investigate the role of nitric oxide (NO) in the mechanism of PAF-induced hearing loss by studying the effects of PAF application on the round window membrane (RWM) with and without PAF-antagonist NO-blocker. Study Design Longitudinal study on randomized guinea pigs using PAF to induce hearing loss. Methods Guinea pigs were divided into four groups: PBS, PAF, PAF-antagonist, and L-NAME. The PBS group received phosphate buffered saline (PBS) and the PAF groups received 10, 20, and 40 ,g of PAF soaked into gelfoam and placed on the RWM. PAF-antagonist (WEB 2170) and NOS inhibitor NG-nitro-l-arginine-methylester (L-NAME) were injected intraperitoneally prior to PAF 20 ,g application on the RWM. The following three tests were performed on each animal group: Hearing was tested with an auditory brainstem response (ABR) test over 24 hours. At the end of 24 hours, cochlear hair cells were examined by scanning electron microscopy (SEM) and immunohistochemistry was carried out on the cochlea to test the expression of inducible nitric oxide synthase (iNOS). Results The PAF group developed significant elevation of ABR threshold and cochlear hair cell damage in the SEM group as compared with the PBS control group. The PAF-antagonist (WEB 2170) and the L-NAME groups did not show significant elevation of ABR threshold and cochlear hair cell damage compared with the group administered PAF 20 ,g, but in the PAF-antagonist group, the elevation of ABR threshold was significant compared with that of the PBS control group, whereas it was not significant compared with the PBS group in the L-NAME group. Strong expression of iNOS on cochlea was observed in the PAF group and lighter expression was seen in PBS, WEB 2170, and L-NAME groups. Conclusions This study demonstrated that PAF placed on the RWM induced hearing loss and cochlear hair cell damage. The PAF-antagonists and L-NAME prevented the PAF-induced hearing loss and inhibited iNOS expression in the cochlea. These findings suggest that the PAF-induced hearing loss caused by cochlear hair cell damage may have been mediated by NO. PAF-antagonists and L-NAME may have future therapeutic implications in preventing sensorineural hearing loss associated with chronic otitis media. The results of this study have significant potential clinical application. [source] Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth muscle cell proliferation: role of nuclear factor-kappa B and cyclin-dependent kinasesCELL PROLIFERATION, Issue 2 2008B. O. Ibe Objective: Platelet-activating factor (PAF) is implicated in pathogenesis of persistent pulmonary hypertension of the neonate (PPHN); PAF is a mitogen for lung fibroblasts. PAF's role in pulmonary vascular smooth muscle cell (PVSMC) proliferation and in hypoxia-induced pulmonary vein (PV) remodelling has not been established and mechanisms for PAF's cell-proliferative effects are not well understood. We investigated involvement of PAF and PAF receptors in PVSMC proliferation. Materials and methods: Cells from pulmonary arteries (SMC-PA) and veins (SMC-PV) were serum starved for 72 h in 5% CO2 in air (normoxia). They were cultured for 24 h more in normoxia or 2% O2 (hypoxia) in 0.1% or 10% foetal bovine serum with 5 µCi/well of [3H]-thymidine, with and without 10 nm PAF. Nuclear factor-kappa B (NF-,B), CDK2 and CDK4 protein expression, and their roles in cell proliferation control were studied. Results: PAF and hypoxia increased SMC-PA and SMC-PV proliferation. WEB2170 inhibited PAF-induced cell proliferation while lyso-PAF had no effect. SMC-PV proliferated more than SMC-PA and PAF plus hypoxia augmented NF-,B protein expression. NF-,B inhibitory peptide attenuated PAF-induced cell proliferation by 50% and PAF increased CDK2 and CDK4 protein expression. The data show that hypoxia and PAF up-regulate PVSMC proliferation via PAF receptor-specific pathway involving NF-,B, CDK2 and CDK4 activations. Conclusion: They suggest that in vivo, in foetal lung low-oxygen environment, where PAF level is high, proliferation of PVSMC will occur readily to modulate PV development and that failure of down-regulation of PAF effects postnatally may result in PPHN. [source] | |||||||||||||