6533b7d8fe1ef96bd126a3df

RESEARCH PRODUCT

Effects of cyclooxygenase-1/cyclooxygenase-2 inhibition on leukocyte/endothelial cell interactions in the rat mesentery.

subject

description

Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase activity and cause gastrointestinal damage in part by promoting leukocyte accumulation in the mucosa. Our aim was to evaluate the effects of selective blockade of the isoenzymes cyclooxygenase-1 and cyclooxygenase-2 on leukocyte adhesion in vivo. Leukocyte/endothelial cell interactions were examined in rat mesenteric venules before and after treatment with indomethacin, SC-560 (5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole, cyclooxygenase-1 inhibitor), DFP (5,5-dimethyl-3-(2-propoxy)-4-(4-methanesulfonyl)-2(5H)-furanone, cyclooxygenase-2 inhibitor), or SC-560 plus DFP (20 mg/kg, i.v. each). Indomethacin increased leukocyte-rolling flux, reduced rolling velocity and elicited significant leukocyte adhesion. Neither SC-560 nor DFP induced these effects although their co-administration reproduced the indomethacin response. Indomethacin and SC-560, but not DFP, abolished cyclooxygenase-1 activity in blood. Plasma from indomethacin- or DFP-, but not from SC-560-treated rats abolished cyclooxygenase-2 activity in activated A549 cells. Specific blockade of cyclooxygenase-1 or cyclooxygenase-2 does not induce any inflammatory event in the rat mesentery and the inflammatory response observed with non-selective NSAIDs seems to be due to the inhibition of both isoenzymes.