Chemotactic properties of ICAM-1 and PECAM-1 on neutrophil granulocytes in ulcerative colitis: effects of prednisolone and mesalazine.
BACKGROUND
ICAM-1 seems to exhibit effects other than passive leucocyte/endothelial interaction.


OBJECTIVE
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 microm; P<0.001), whereas PECAM-1 attracted neutrophils equally in the range of 0.1-10 nM (25.0 microm; 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.
Department of Medicine M, Division of Gastroenterology, Glostrup Hospital, University of Copenhagen, Denmark. ben.vainer@dadlnet.dk
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B
Vainer
O H
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Nielsen
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology*; D019804:Mesalamine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000494:pharmacology*; D011239:Prednisolone / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019804:Mesalamine; D011239:Prednisolone