Platelet-activating factor-induced ischemic bowel necrosis: the effect of platelet-activating factor acetylhydrolase.
In the present investigation, the rat model of necrotizing enterocolitis (NEC) was further developed by injection of platelet-activating factor (PAF) in the descending aorta. The role of the plasma PAF-acetylhydrolase (PAF-AH) was examined in the prevention of this disease. PAF (0.35 micrograms) caused ischemic intestinal necrosis when administered intraaortically. The effects of PAF injection on the small intestine were examined histologically in samples of the duodenum, jejunum, and ileum. The administration of PAF resulted in extensive hemorrhagic damage in all regions of the small bowel and a marked hemoconcentration. Pretreatment of the rats with dexamethasone or medroxyprogesterone significantly increased plasma PAF-AH activity. Dexamethasone and medroxyprogesterone prevented the gross and histologic features of NEC as well as the hemoconcentration. In contrast, lower amounts of PAF were sufficient to cause bowel necrosis and hemoconcentration when decreased activities of plasma PAF-AH were induced by 17 alpha-ethynylestradiol or 4-aminopyrazolopyrimidine administration. We have recently reported that PAF-AH is present in human milk. The beneficial effect of breast feeding in preventing the development of NEC in the newborn is discussed and a mechanism proposed to explain this finding. It is suggested that PAF may play an important role in the pathogenesis of NEC and that the increased plasma activity of PAF-AH caused by dexamethasone and the presence of this enzyme, of milk origin, in the lumen of the small bowel may prove to be beneficial in the prevention of this disease.
Furukawa
M
M
Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas 75235-9051.
Lee
E L
EL
Johnston
J M
JM
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007422:Intestines / Q000098:blood supply* / Q000473:pathology*; D007511:Ischemia / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D008895:Milk, Human / Q000201:enzymology; D009336:Necrosis; D010741:Phospholipases A / Q000097:blood*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D010972:Platelet Activating Factor; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase