Gelatinase Contributes to the Degradation of Glomerular Basement Membrane Collagen by Human Neutrophils

Abstract

Neutrophils contain a number of proteinases active at neutral pH which are able todegrade extracellular matrices. We have determined the contribution of the major neutral proteinases to human neutrophil-mediated degradation of glomerular basement membrane type IV collagen in an in vitro model of immune complex-induced injury. Studies with proteinase inhibitors showed that with intact neutrophils stimulated by immune complexes trapped within the basement membrane, approximately 70% of the degradation was due to serine proteinases and 30% to metalloproteinases. Identical results were obtained with cell-free medium containing neutrophil granule contents. Elastase accounted for almost all the digestion by serine proteinases with a minimal contribution by cathepsin G. All the metalloproteinase activity was due to gelatinase rather than collagenase, and purified gelatinase was also shown to degrade basement membrane collagen. Hence, gelatinase has activity against type IV collagen and may be able to degrade collagens not cleaved by specific collagenases.