Platelet activating factor responses

Dhar A, Shukla SD. Electrotranqection of pp60v-src monoclonal antibcxly inhibits activation of phospholipase C in platelets. A new mechanism for platelet-activating factor responses. J Biol Chem 1994 269 9123-9127... 

Platelet activating factor (PAF) was first identified by its ability (at low levels) to cause platelet aggregation and dilation of blood vessels, but it is now known to be a potent mediator in inflammation, allergic responses, and shock. PAF effects are observed at tissue concentrations as low as 10 M. PAF causes a dramatic inflammation of air passages and induces asthma-like symptoms in laboratory animals. Toxic-shock syndrome occurs when fragments of destroyed bacteria act as toxins and induce the synthesis of PAF. This results in a drop in blood pressure and a reduced... 

Ali H, Fisher 1, Haribabu B, Richardson RM and Snyderman R (1997) Role of phosphohpase Cbeta3 phosphorylation in the desensitization of cellular responses to platelet-activating factor. 1 Biol Chem 272(18) 11706-11709... 

Platelet-activating factor A mediator of platelet aggregation and inflammation that is produced in response to stimuli, such as white blood cells. 

It is possible that nematode-secreted AChEs act on alternative substrates to ACh. We had previously suggested, on the basis of structural similarity, that platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, might represent such an alternative substrate (Blackburn and Selkirk, 1992b) but subsequent studies demonstrated that purified AChEs did not cleave PAF, and the enzyme responsible for this activity in secreted products of N. brasiliensis, PAF acetylhydrolase, was purified and defined as a distinct heterodimeric protein (Grigg et al., 1996). Although an open mind on the subject sould be kept, the strict substrate specificity of the nematode-secreted AChEs suggests that they most likely act on ACh alone. 

Mast cell degranulation in response to allergens results in release of mediators such as histamine eosinophil, and neutrophil chemotactic factors leukotrienes C4, D4, and E4 prostaglandins and platelet-activating factor (PAF). Histamine is capable of inducing smooth muscle constriction and bronchospasm and may play a role in mucosal edema and mucus secretion. 

Gardner, C.R., Laskin, J.D., and Laskin, D.L., Distinct biochemical responses of hepatic macrophages and endothelial cells to platelet-activating factor during endotoxemia, J. Leukoc. Biol., 57, 269, 1995. 

Nilsson, G., Metcalfe, D. D., and Taub, D. D., Demonstration that platelet-activating factor is capable of activating mast cells and inducing a chemotactic response, Immunology 99, 314-319, 2000. 

Chung KF, Dent G, McCuster M, Guinot P, Page CP, Barnes PJ. Effect of ginkgolide mixture (BN 52063) in antagonizing skin and platelet responses to platelet activating factor in man. Lancet 1987 1 248-251. 

In addition to their effects on leukocyte function, glucocorticoids influence the inflammatory response by reducing the prostaglandin, leukotriene, and platelet-activating factor synthesis that results from activation of phospholipase - Finally, glucocorticoids reduce expression... 

LPS can provoke a multi-organ failure, due to the secretion of acute-phase reactants such as platelet-activating factor (PAF), TNF-a, and LBP. Multi-organ failure is also due to the secretion of prostaglandin E2 (PGE2) and inflammatory cytokines such as TNF-a, IL-ip, IL-6, whose production may increase the secretion of the acute-phase reactant, LBP [63], thus constituting an amplifying loop. The presence of a tumor may modify this host response as will be discussed below. 

Cysteinyl leukotrienes and platelet-activating factors released by eosinophils injure mucosal surfaces of the airways. Furthermore, they damage M2 muscarinic receptors and as a result the cholinergic response is unchecked in the absence of inhibitory M2 muscarinic receptors. The production of eosinophils is regulated... 

Shigematsu S, Ishida S, Hara M, Takahashi N, Yoshimatsu H, Sakata T, Korthuis RJ. 2003. Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants. Free Radic Biol Med 34 810-817. 

---