Cocaine interacts with macrophages to modulate mesangial cell proliferation

J Mattana, N Gibbons and PC Singhal

Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York.

Human immunodeficiency virus infection is associated with the development of focal segmental glomerulosclerosis (FSGS). The majority of these patients with renal disease, however, are also cocaine abusers, but it is unknown what role cocaine may play in the development of focal segmental glomerulosclerosis. We undertook the present study to determine in vitro whether cocaine can modulate mesangial cell (MC) proliferation, a process believed to be a precursor to the development of glomerulosclerosis, either directly or indirectly via interaction with macrophages (M phi). Cocaine alone was not found to alter significantly either MC number or MC [3H]thymidine incorporation. However, when MC were incubated with secretory products collected from M phi preincubated with standard medium or medium containing cocaine, MC proliferation was found to be significantly enhanced with secretory products from M phi preincubated with cocaine in both serum-free (P < .001) and serum-stimulated conditions (P < .001). The effect of cocaine was found to be concentration-related. Pretreatment of macrophage secretory products from cocaine-treated M phi with neutralizing antibodies to transforming growth factor-beta significantly augmented the mitogenic effect of cocaine macrophage secretory products, and neutralizing antibodies to interleukin-6 significantly attenuated this effect. Direct incubation of MC with transforming growth factor-beta and interleukin-6 caused significant suppression and augmentation of MC proliferation, respectively. These data suggest that cocaine can modulate MC proliferation via interaction with M phi and that interleukin-6 and transforming growth factor-beta participate in this modulating effect. These results support a potential role for cocaine in the development of focal segmental glomerulosclerosis in patients with human immunodeficiency virus infection.

Volume 271, Issue 1, pp. 311-318, 10/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics

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