B Vainer1, O H Nielsen. 1. Department of Medicine M, Division of Gastroenterology, Glostrup Hospital, University of Copenhagen, Denmark. ben.vainer@dadlnet.dk
Abstract
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 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.
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 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 colitispatients 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.
Authors: Jennifer A Dewhurst; Simon Lea; Elizabeth Hardaker; Josiah V Dungwa; Arjun K Ravi; Dave Singh Journal: Sci Rep Date: 2017-08-02 Impact factor: 4.379