Requirement for macrophages in neuronal injury induced by HIV envelope protein gp120

Abstract

Hiv-1-related neuronal injury may involve a complex web of viral proteins and cytokines, but neurons themselves are not infected. The HIV envelope protein gpl20 has been shown to engender an early increase in neuronal free calcium followed by delayed excitotoxic-Iike damage, which is prevented by N-methyl-D-aspartate (NMDA) antagonists. In the present study, we found that the injurious effects of gpl20 on retinal ganglion cell neurons require the presence of macrophages in mixed neuronal-glial cultures of postnatal retina. Within 24 hours of incubation, 20 pM gpl20 injured nearly 40% of retinal ganglion cells in cultures containing macrophages and other glial cells, whereas no deleterious effects of gpl20 were noted on retinal ganglion cells in cultures depleted of macrophages. Thus, the toxic effect of gpl20 on neurons appears to be an indirect one, mediated by activation of macrophages and perhaps other glial cells. © Rapid Communication Of Oxford Ltd.