Neutrophil extracellular trap-related extracellular histones cause vascular necrosis in severe GN

SVR Kumar, OP Kulkarni, SR Mulay… - Journal of the …, 2015 - journals.lww.com
Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a
local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from
calf thymus or histones released by neutrophils undergoing NETosis killed glomerular
endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner.
Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin
prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 …