Effects of proteinase inhibitors on polymorphonuclear neutrophil polarization.

Polarization of polymorphonuclear neutrophils (PMNs) can be elicited by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) and the microtubule-disrupting compound colchicine. Here we report on whether natural and synthetic proteinase inhibitors alter the polarizing response to these two agents. The alpha 1-proteinase inhibitor, N-tosyl-L-phenylalanine chloromethyl ketone, and N alpha-tosyl-L-lysine chloromethyl ketone suppress fMLP-induced polarization and locomotion in a dose-dependent fashion, but none of them affects colchicine-induced polarization. We suggest that proteinase inhibitors suppress fMLP-induced polarization by blocking cell surface proteinases that generate an intracellular signal for cytoskeletal change and polarization.