Effect of nonsteroidal anti-inflammatory drugs on LFA-1 and ICAM-1 expression in gastric mucosa.
Leukocyte adhesion to the endothelium appears to play an important role in gastric injury. This study aimed to develop immunohistochemical staining techniques to investigate the distribution and sequence of expression of both leukocyte [lymphocyte function associated antigen 1 (LFA-1)] and endothelial [intracellular adhesion molecule 1 (ICAM-1)] adhesion molecules in the mucosa after treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). In control rats there were 803 +/- 72 LFA-1-stained cells/mm2 in the deep mucosa, 134 +/- 32 cells/mm2 in the superficial mucosa, and 6.4 +/- 1.2 ICAM-1-stained blood vessels/mm2 in the total mucosa. The number of ICAM-1-stained blood vessels in the mucosa increased significantly after 30 min of treatment with intragastric aspirin (30 mM; 25.2 +/- 7.2/mm2, P < 0.01) and indomethacin (20 mg/kg; 20.7 +/- 4.4/mm2, P < 0.01) before any appreciable mucosal damage was evident. This increase was reversed by treatment with misoprostol (100 micrograms/kg) in both aspirin- (7.6 +/- 1.7/mm2, P < 0.01) and indomethacin-treated animals (10.7 +/- 2.6/mm2, P < 0.05). There was no significant increase in LFA-1-positive cells until 60 min of NSAID treatment. We conclude that the adhesion molecules LFA-1 and ICAM-1 are expressed in the normal gastric mucosa and that the number of ICAM-1-stained blood vessels increase rapidly after NSAID treatment. This increase in ICAM-1 expression may be associated with an inhibition of prostaglandin synthesis by NSAIDs. These results provide further support for the role of early vascular changes in NSAID gastropathy.
Andrews
F J
FJ
Department of Surgery, Monash Medical School, Alfred Hospital, Prahran, Victoria, Australia.
Malcontenti-Wilson
C
C
O'Brien
P E
PE
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007213:Indomethacin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008297:Male; D016595:Misoprostol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013194:Staining and Labeling
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016595:Misoprostol; D018799:Intercellular Adhesion Molecule-1; D001241:Aspirin; D007213:Indomethacin