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Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene
Author(s) -
Tranchina Salvatore,
Bernasconi Sergio,
Dejana Elisabetta,
Maschio Aldo
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14776.x
Subject(s) - monocyte , chemistry , adhesion , integrin , cell adhesion , tumor necrosis factor alpha , umbilical vein , paraformaldehyde , microbiology and biotechnology , pharmacology , receptor , biochemistry , immunology , biology , in vitro , organic chemistry
1 The ability of the coumarin derivative cloricromene (8‐monochloro‐3‐β‐diethylaminoethyl‐4‐methyl‐7‐ethoxy‐carbonylmethoxycoumarin) to inhibit monocyte adhesion to human cultured umbilical vein endothelial cells (HUVEC) was investigated. 2 Cloricromene (10–200 μ m ) inhibited, in a concentration‐dependent manner, the adhesion of both resting and activated monocytes to HUVEC. Significant inhibition was reached with drug concentrations ranging between 15 to 30 μ m . 3 The inhibitory activity was, at least in large part, directed to monocytes since no inhibition was observed after selective preincubation of HUVEC with cloricromene and the drug maintained its effect also on monocyte adhesion to paraformaldehyde‐treated HUVEC. 4 Inhibition was maximal after 1 min of exposure of monocytes to cloricromene and persisted even in the absence of the drug. 5 Both basal and chemoattractant‐mediated monocyte adhesion was inhibited by cloricromene as it was by TS1/18, a monoclonal antibody (mAb) directed to β2 integrins; however, cytofluorimetric analysis showed that cloricromene was unable to modulate the expression of β2 integrins on the monocyte surface. 6 When monocyte adhesion was mediated by a large set of adhesive receptors, as obtained after treatment of HUVEC with either interleukin 1β (IL‐1; 50 ng ml −1 ) or tumour necrosis factor‐α (TNF; 100 u ml −1 ), the inhibitory effect of cloricromene was considerably reduced. 7 The results of this study show that cloricromene may regulate monocyte adhesion to HUVEC, an event relevant in vivo in the pathogenesis of inflammatory and atherosclerotic processes.