Mechanism of prostaglandin E2 inhibition of acute changes in vascular permeability.
In order to determine the mechanism of antiinflammatory activity, prostaglandin E2 (PGE2) or diluent was administered to rats 2 h prior to intradermal injections of various mediators of inflammatory vascular permeability changes. Vascular permeability was measured as the accumulation of [125I]rat serum albumin at the site of mediator injunction. PGE2 at 500 micrograms significantly inhibited protein leakage produced by histamine, platelet activating factor, zymosan, and zymosan-activated plasma. Pretreatment with PGE2 had no effect on protein leakage induced by injection of lysosomal enzymes, glucose oxidase, or xanthine oxidase. The accumulation of polymorphonuclear leukocytes (PMNs) at the site of injection of zymosan or zymosan-activated plasma was not altered by PGE2 administration. In separate experiments, the ability of PGE2 to alter phagocytosis and oxygen radical production by PMN was examined. PGE2 significantly inhibited phagocytosis at 2 h, but this returned to normal by 6 h. Production of hydrogen peroxide by PMN was not affected by PGE2. These results suggest that PGE2 prevents acute changes in vascular protein leakage by preventing endothelial cell contraction and by inhibiting specific PMN functions.
McLeish
K R
KR
Department of Medicine, University of Louisville School of Medicine, Kentucky.
Wellhausen
S R
SR
Stelzer
G T
GT
D000818:Animals; D000936:Antigen-Antibody Complex / Q000008:administration & dosage; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003167:Complement Activation / Q000187:drug effects; D015232:Dinoprostone; D004730:Endothelium, Vascular / Q000187:drug effects*; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism; D015054:Zymosan / Q000009:adverse effects
D000936:Antigen-Antibody Complex; D011458:Prostaglandins E; D013481:Superoxides; D015054:Zymosan; D015232:Dinoprostone