Tumor necrosis factor increases the elastolytic potential of adherent neutrophils: a role for hypochlorous acid.

Neutrophils adhered to biologic surfaces exhibit proteolytic cleavage of surface proteins even in the presence of proteinase inhibitors. Such proteolysis is restricted to the pericellular space and appears to require the dual action of proteinases and reactive oxygen species. The present study was designed to investigate the mechanism by which tumor necrosis factor-α (TNF) stimulates neutrophil proteolysis. Tissue culture wells were coated with insoluble 3H-labeled elastin substrate. Human blood neutrophils (0.5 to 2.0 × 106 cells/ml/well) were incubated in the coated wells for 4 to 18 h at 37°C in the presence of varying concentrations of serum or purified α1-antitrypsin (A1AT). TNF (0 to 1,000 U/ml) was also present in the incubations. Elastin degradation was determined as soluble 3H-elastin fragments released into the supernatants. As previously reported, cells (no TNF) exhibited spontaneous elastolysis even in the presence of 1% serum or 4 µM A1AT. Compared with cells incubated alone (no TNF), TNF inc...