INDOMETHACIN-INDUCED LEUKOCYTE ADHESION IN MESENTERIC VENULES - ROLE OF LIPOXYGENASE PRODUCTS

被引:215
作者
ASAKO, H
KUBES, P
WALLACE, J
GAGINELLA, T
WOLF, RE
GRANGER, DN
机构
[1] LOUISIANA STATE UNIV,DEPT MED,SHREVEPORT,LA 71130
[2] LOUISIANA STATE UNIV,CTR EXCELLENCE ARTHRIT & RHEUMATOL,SHREVEPORT,LA 71130
[3] SEARLE RES & DEV,SKOKIE,IL 60077
[4] UNIV CALGARY,GASTROINTESTINAL RES GRP,CALGARY T2N 1N4,ALBERTA,CANADA
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1992年 / 262卷 / 05期
关键词
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTACYCLIN; LEUKOCYTE ADHERENCE AND EMIGRATION; MISOPROSTOL; LEUKOTRIENES;
D O I
10.1152/ajpgi.1992.262.5.G903
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Although the pathogenetic mechanisms underlying indomethacin-induced mucosal injury remain undefined, the results from recent studies suggest that leukocyte adherence in gastric microvessels may be an important component of this injury process. The objective of this study was to determine whether clinically relevant plasma concentrations of indomethacin promote leukocyte-endothelial cell adhesive interactions in postcapillary venules. Erythrocyte velocity, vessel diameter, leukocyte rolling velocity, and the number of adherent (stationary for greater-than-or-equal-to 30 s) and emigrated leukocytes were measured in rat mesenteric venules. Repeat measurements of all parameters were obtained within 20 min after addition of either 2.5 or 25-mu-g/ml indomethacin to the mesenteric superfusate. In some experiments, rats were pretreated with either a leukotriene (LT) synthesis inhibitor (L 663,536), an LTD4 (MK-571) or LTB4 (SC 41930) receptor antagonist, misoprostol, or prostacyclin (PGI2). Indomethacin alone increased the number of adherent leukocytes, reduced both leukocyte rolling velocity and venular shear rate, but did not promote leukocyte emigration. L 663,536 and SC 41930 prevented all of the adhesive and hemodynamic alterations induced by indomethacin; misoprostol and PGI2, but not MK-571, exerted similar beneficial effects. These results indicate that indomethacin promotes leukocyte adherence in postcapillary venules through an LTB4-dependent mechanism.
引用
收藏
页码:G903 / G908
页数:6
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