Modulation of fibroblast-induced clot retraction by calcium channel blocking drugs and the monoclonal antibody ALB6.
Suspensions of living human fibroblast induce fibrin clot retractile activity (FCR). The efficiency is dependent on the growth phase; it is maximal during active growth and reduced in post-confluent cultures. In contrast human osteosarcoma cells constantly exhibit very low FCR efficiency. Two different calcium channel-blocking drugs Diltiazem and Verapamil inhibit, depending on the concentrations employed, FCR, and spreading within the clots of the normal cells. Intermediate FCR levels are associated with intermediate degrees of spreading. A similar dose dependent inhibition is also obtained by treating the normal cells with the calmodulin inhibitor trifluoperazine (TFP). On the other hand, treatment of the normal cells with the monoclonal antibody ALB6 which is directed at the human leukocyte differentiation antigen CD9 (p24) causes a significant increase in the FCR efficiency in post-confluent normal cells, but it has no effect on the Te85 osteosarcoma cells. Moreover ALB6 IgG reverses the FCR inhibitory effect of the calcium-channel blocking drugs but not that of TFP. This means that the ALB6 IgG target on the cellular membrane is probably the same as that of the two drugs and that ALB6 IgG is active in the regulation of the calcium flux which controls fibrin clot retractile activity of normal human fibroblasts.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002460:Cell Line; D003018:Clot Retraction; D005337:Fibrin / Q000502:physiology; D005347:Fibroblasts / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012516:Osteosarcoma / Q000503:physiopathology; D014268:Trifluoperazine / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D002121:Calcium Channel Blockers; D002147:Calmodulin; D007074:Immunoglobulin G; D014268:Trifluoperazine; D005337:Fibrin