Suppression by apoptotic cells defines tumor necrosis factor-mediated induction of glomerular mesangial cell apoptosis by activated macrophages

Abstract

Activated macrophages (MΦ) isolated from inflamed glomeruli or generated by interferon-γ and lipopolysaccharide treatment in vitro induce glomerular mesangial cell apoptosis by hitherto incompletely understood mechanisms. In this report we demonstrate that nitric oxide-independent killing of co-cultured mesangial cells by interferon-γ/lipopolysaccharide-activated MΦ is suppressed by binding/ingestion of apoptotic cells and is mediated by tumor necrosis factor (TNF). Thus, soluble TNF receptor-1 significantly inhibited induction of mesangial cell apoptosis by 1) rodent MΦ in the presence of nitric oxide synthase inhibitors or 2) human MΦ, both situations in which nitric oxide release was mini..