Quantification of distinct molecular species of platelet activating factor in ulcerative colitis

Abstract

The aim of this study was to characterize the synthesis and metabolism of platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) by colonic mucosa from patients with ulcerative colitis and healthy individuals. Tissue was obtained by endoscopic biopsy and by scraping the mucosa from surgical resections. Tissue was assayed for the various molecular species of PAF and its biologically inactive metabolite lyso-PAF using gas chromatography/mass spectrometry. Mucosa from surgical resections for ulcerative colitis contained C16:0 PAF (mean = 156 ng/g of mucosa), but not C18:0 PAF, PAF was not identified in mucosa from normal surgical resections or in endoscopic biopsies from either patients with ulcerative colitis or normal individuals. Both C16:0 lyso-PAF and C18:0 lyso-PAF were found in mucosa from normal and ulcerative colitis surgical resections and in endoscopic biopsies from ulcerative colitis and normal tissue. Levels of lyso-PAF were similar in ulcerative colitis and normal mucosa. Incubation of mucosa from areas of active inflammation in ulcerative colitis with the calcium ionophore A23187 increased the levels of C16:0 PAF by 2-3 fold and also increased the levels of C16:0 lyso-PAF. Addition of 3H-PAF to endoscopic biopsies from either normal individuals or patients with ulcerative colitis resulted in hydrolysis to 3H-lyso-PAF. The data on colonic mucosal levels of PAF are consistent with the results of earlier studies measuring PAF in patients with ulcerative colitis by bioassay. This study examines the synthesis and metabolism of specific molecular species of PAF in ulcerative colitis for the first time.

The intestinal anti‐inflammatory effect of dersalazine sodium is related to a down‐regulation in IL‐17 production in experimental models of rodent colitis

“…According to these results, an early inhibition in IL‐17 production seems to be necessary for the intestinal anti‐inflammatory activity of DS, an effect that could be ascribed to its PAF antagonist activity. PAF is a potent pro‐inflammatory phospholipid mediator that has been implicated in inducing intestinal inflammation in diseases such as IBD (Sobhani et al ., 1992; Thyssen et al ., 1996) and necrotizing enterocolitis (Hsueh et al ., 2003). It is released early in inflammation by a variety of cell types and acts mainly after binding to its receptor, PAF‐R, a GPCR found on a variety of cells, including cells of the immune system (Chao and Olson, 1993).…”

A soybean and fish oil mixture with different n-6/n-3 PUFA ratios modulates the inflammatory reaction in mice with dextran sulfate sodium-induced acute colitis

“…Several studies showed that dietary fish oil and n-3 PUFAs have immunomodulatory effects and therapeutic benefits in various diseases and metabolically stressed conditions [2,3]. Inflammatory lipid mediators and cytokines participate in the development of chronic lesions of CD and UC [4,5]. n-3 PUFAs may alter eicosanoid formation, thus reducing inflammatory cytokine generation [6].…”

Platelet-Activating Factor Regulates Chloride Transport in Colonic Epithelial Cell Monolayers

“…Indeed, cultured colonic biopsies from ulcerative colitis patients have been shown to produce PAF (40) at 0.8 nmol/g (tissue) /h rates. In another study, tissue concentrations of PAF in micromolar concentrations were found in mucosal scrapings of biopsy specimens from patients with ulcerative colitis (41). Escherichia coli and other bacteria that are commonly found in the gastrointestinal tract are also extremely capable of producing PAF (42,43).…”