EFFECT OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON LFA-1 AND ICAM-1 EXPRESSION IN GASTRIC-MUCOSA

Leukocyte adhesion to the endothelium appears to play an important rol e in gastric injury. This study aimed to develop immunohistochemical s taining techniques to investigate the distribution and sequence of exp ression of both leukocyte [lymphocyte function associated antigen 1 (L FA-1)] and endothelial [intracellular adhesion molecule 1 (ICAM-1)] ad hesion molecules in the mucosa after treatment with nonsteroidal anti- inflammatory drugs (NSAIDs). In control rats there were 803 +/- 72 LFA -1-stained cells/mm(2) in the deep mucosa, 134 +/- 32 cells/mm(2) in t he superficial mucosa, and 6.4 +/- 1.2 ICAM-1-stained blood vessels/mm (2) in the total mucosa. The number of ICAM-1-stained blood vessels in the mucosa increased significantly after 30 min of treatment with int ragastric aspirin (30 mM; 25.2 +/- 7.2/mm(2), P < 0.01) and indomethac in (20 mg/kg; 20.7 +/- 4.4/mm(2), P < 0.01) before any appreciable muc osal damage was evident. This increase was reversed by treatment with misoprostol (100 mu g/kg) in both aspirin- (7.6 +/- 1.7/mm(2), P < 0.0 1) and indomethacin-treated animals (10.7 +/- 2.6/mm(2), P < 0.05). Th ere was no significant increase in LFA-1-positive cells until 60 min o f NSAID treatment. We conclude that the adhesion molecules LFA-1 and I CAM-1 are expressed in the normal gastric mucosa and that the number o f ICAM-1-stained blood vessels increases rapidly after NSAID treatment . This increase in ICAM-1 expression may be associated with an inhibit ion of prostaglandin synthesis by NSAIDs. These results provide furthe r support for the role of early vascular changes in NSAID gastropathy.