Role of calcium and calmodulin in the activation of murine peritoneal macrophages with cisplatin.
When fura-2/AM loaded peritoneal macrophages were treated with cisplatin, it resulted in a rapid increase in the intracellular free calcium. Calcium modulating agents, EGTA, nifedipine, and TMB-8, and the calmodulin antagonist W-7 inhibited cisplatin-induced tumoricidal activity of murine peritoneal macrophages. Supernatants collected from macrophages treated with cisplatin and EGTA, nifedipine, TMB-8 or W-7 demonstrated decreased tumor necrosis factor (TNF) and interleukin-1 (IL-1) activity in comparison to supernatants collected from macrophages treated with cisplatin alone. Similarly, TNF and IL-1 activity were significantly inhibited in paraformaldehyde (PFA)-fixed macrophages and freeze-thaw lysates of macrophages treated with cisplatin and different calcium and calmodulin-modulating agents. These results suggest that calcium and calmodulin are important in the cisplatin-mediated activation of murine peritoneal macrophages to tumoricidal state.
Sodhi
A
A
School of Biotechnology, Banaras Hindu University, Varanasi, India.
Kumar
R
R
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D002945:Cisplatin / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009543:Nifedipine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D002147:Calmodulin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D004533:Egtazic Acid; D009543:Nifedipine; D002945:Cisplatin; D002118:Calcium