In vitro inhibition of human polymorphonuclear cell function by cloricromene.
Cloricromene, a coumarin derivative with antiaggregating and vasodilating properties, was tested in vitro on polymorphonuclear cell (PMN) adhesion to the endothelium, superoxide anion generation and chemotaxis. PMN adhesion was measured using cultured human umbilical vein endothelial cells (EC) either untreated or previously activated with interleukin-1 (IL-1). Cloricromene (5-50 microM) induced dose-related inhibition of PMN adhesion to untreated and IL-1 treated EC. Cloricromene also inhibited PMN superoxide generation induced by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or by N-formyl-methionyl-leucyl-phenylalanine (FMLP). PMN and monocyte chemotaxis was evaluated by a modification of the Boyden chamber technique. Cloricromene inhibited both types of cell motility induced by FMLP in a concentration-dependent fashion. The major cloricromene metabolite (cloricromene acid) had no effect on any of the biological parameters studied up to a concentration of 500 microM. HPLC measurement showed that cloricromene accumulated in PMN within a few minutes and levels of the drug were still high after 60 min. In contrast its acid metabolite was not taken up in a significant amount during incubation periods up to 60 min. We conclude that cloricromene inhibits a series of PMN activities in vitro. This effect might be of pharmacological interest in view of the role of PMN activation in different pathophysiological conditions.
Bertocchi
F
F
Mario Negri Institute for Pharmacological Research, Milano, Italy.
Breviario
F
F
Proserpio
P
P
Wang
J M
JM
Ghezzi
P
P
Travagli
R A
RA
Prosdocimi
M
M
Dejana
E
E
D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002860:Chromium Radioisotopes; D002866:Chromonar / Q000031:analogs & derivatives / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007957:Leukocyte Adherence Inhibition Test; D009504:Neutrophils / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D002860:Chromium Radioisotopes; D003374:Coumarins; D005343:Fibrinolytic Agents; D007375:Interleukin-1; D014665:Vasodilator Agents; D013481:Superoxides; C025945:cloricromen; D002866:Chromonar