Neutrophils degrade subendothelial matrices in the presence of alpha-1-proteinase inhibitor. Cooperative use of lysosomal proteinases and oxygen metabolites.

Triggered neutrophils rapidly degraded labeled matrices secreted by cultured, venous endothelial cells via a process dependent on elastase but not oxygen metabolites. In the presence of high concentrations of alpha-1-proteinase inhibitor, the ability of the stimulated neutrophil to solubilize the matrix was impaired. However, at lower concentrations of alpha-1-proteinase inhibitor the neutrophil could enhance the degradative potential of its released elastase by a H2O2-dependent process. Coincident with this increase in matrix damage, the stimulated neutrophil destroyed the elastase inhibitory activity of the alpha-1-proteinase inhibitor via a catalase-inhibitable process. The ability of the triggered neutrophil to solubilize the matrix in the presence of alpha-1-proteinase inhibitor was unaffected by superoxide dismutase or hydroxyl radical scavengers but was markedly impaired by catalase, azide, or hypochlorous acid scavengers. We conclude that neutrophils can cooperatively use an oxidant with characteristics similar, if not identical, to hypochlorous acid and the lysosomal proteinase elastase to negate the protective effects of alpha-1-proteinase inhibitor in order to attack the subendothelial matrix.