Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene.
1. The ability of the coumarin derivative cloricromene (8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy- carbonylmethoxycoumarin) to inhibit monocyte adhesion to human cultured umbilical vein endothelial cells (HUVEC) was investigated. 2. Cloricromene (10-200 microM) 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 microM. 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 beta 2 integrins; however, cytofluorimetric analysis showed that cloricromene was unable to modulate the expression of beta 2 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 1 beta (IL-1; 50 ng ml-1) or tumour necrosis factor-alpha (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.
Tranchina
S
S
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Bernasconi
S
S
Dejana
E
E
Del Maschio
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002866:Chromonar / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D005470:Fluorometry; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects*; D011247:Pregnancy; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects / Q000276:immunology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
D000911:Antibodies, Monoclonal; D016028:Receptors, Leukocyte-Adhesion; C025945:cloricromen; D002866:Chromonar