Platelet-activating factor (PAF) up-regulates plasma and tissue PAF-acetylhydrolase activity in the rat : Effect of cycloheximide

• Published in: Pediatric research Vol. 42; no. 5; pp. 597 - 603
• Main Authors: WANG, H, TAN, X.-D, QU, X.-W, CHANG, H, REMICK, D. G, GONZALEZ-CRUSSI, F, HSUEH, W
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.11.1997
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Cycloheximide - pharmacology; Emergency and intensive care: neonates and children. Prematurity. Sudden death; Intensive care medicine; Intestines - metabolism; Intestines - pathology; Male; Medical sciences; Necrosis; Phospholipases A - blood; Platelet Activating Factor - physiology; Protein Biosynthesis; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Up-Regulation; Human; Animal model; Rat; Enzyme; Pathogenesis; Rodentia; Necrotizing enterocolitis; Esterases; Platelet activating factor; Carboxylic ester hydrolases; Vertebrata; 1-Alkyl-2-acetylglycerophosphocholine esterase; Regulation(control); Mammalia; Newborn; Enzymatic activity; Digestive diseases; Hydrolases; Intestinal disease
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/00006450-199711000-00008

Platelet-activating factor (PAF) is a proinflammatory phospholipid mediator implicated in necrotizing enterocolitis. Regulation of PAF-acetylhydrolase (AH), the enzyme degrading PAF, is poorly understood. In this study we found that administration of a dose of PAF (1.5 microg/kg, i.v.), which does not cause gross intestinal injury, increased plasma and intestinal PAF-AH in the rat. Cycloheximide (CHX, 5 mg/kg, i.v.) reduced the activity of plasma (but not intestinal tissue) AH in control, as well as in PAF-injected rats, and aggravated systemic inflammation and tissue injury in the latter. The intestinal necrosis induced by PAF and CHX was ameliorated by posttreatment with WEB2170 (a PAF antagonist), indicating a role of endogenous PAF in mediating injury. Both WEB2170 and anti-TNF antibody reduced PAF-induced AH activity in intestinal tissue, but not in the plasma. Allopurinol largely prevented the injury induced by PAF and CHX, but had no effect on the up-regulation of AH. We conclude: 1) de novo protein synthesis is required to maintain physiologic AH level in the plasma; 2) PAF up-regulates plasma and intestinal AH activity; 3) CHX enhances the injurious effect of PAF; 4) endogenous PAF and TNF also play a role in the up-regulation of intestinal AH; the former probably mediating the intestinal injury by PAF; and 5) reactive oxygen species may mediate the injurious effect of PAF plus CHX, but do not contribute to the regulation of AH by PAF.