Chemotactic properties of ICAM-1 and PECAM-1 on neutrophil granulocytes in ulcerative colitis: Effects of prednisolone and mesalazine
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Background: ICAM-1 seems to exhibit effects other than passive leucocyte/endothelial interaction. Aim: To investigate the attracting properties of selected adhesion molecules, assessing the influence of the two major anti-inflammatory drugs in ulcerative colitis, prednisolone and mesalazine. Methods: Circulating neutrophils (11 ulcerative colitis, 15 controls) were assessed in microchemotaxis chambers by the leading front technique, using physiologically relevant concentrations of ICAM-1 (0.005-5000 pM), PECAM-1 (0.001-1000 nM), and P-selectin (0.01-100 nM). Neutrophils pre-incubated with prednisolone (10-8-10-4 M) or mesalazine (0.65-10.4 nM) were assessed towards ICAM-1. Results: Migration of neutrophils towards ICAM-1 showed a bell-shaped curve with a maximum at 5 pM (migration: 37.7 μm; P < 0.001), whereas PECAM-1 attracted neutrophils equally in the range of 0.1-10 nM (25.0 μm; P < 0.001). P-selectin had no cell-attracting effect. No differences were detected between cells from ulcerative colitis patients and controls. Pre-treatment with prednisolone decreased the cell attracting effect of ICAM-1 in a dose-dependent manner to 72% of the basal migration (P < 0.001). Conversely, prednisolone showed a pro-chemokinetic effect by increasing the spontaneous locomotion of neutrophils by 40% (P < 0.001). Conclusions: Specific chemotactic properties were observed for ICAM-1 and PECAM-1. Prednisolone exhibited a dual effect in inhibiting the ICAM-1-mediated migration and stimulating the general locomotion of neutrophils.
|Journal||Alimentary Pharmacology and Therapeutics|
|Number of pages||9|
|Publication status||Published - 24 Aug 2000|