PROTEOLYTIC POTENTIAL OF HUMAN NEUTROPHIL MEMBRANES

A synergistic role for proteases in the degradation of extracellular m atrix proteins has been proposed, Plasma membrane was isolated from a neutrophil homogenate, on a sucrose gradient, and shown to activate ge latinolysis when purified 92 kDa gelatinase was added to the medium. T his stimulatory activity was enhanced by the addition of phorbol 12-my ristate 13-acetate (PMA) in a dose-dependent manner, and was partially sensitive to phenylmethylsulfonyl fluoride treatment. The effect was abolished by the addition of 1 M KCl or 0.05% Brij 35 extraction. Both elastase and urinary type plasminogen activator were shown to be invo lved in the process. Moreover, upon neutrophil stimulation by PMA, 92 kDa gelatinase, as elastase, became associated with the plasma membran e, as shown by a subcellular fractionation experiment. These in vitro observations suggest that human neutrophils may be able, in vivo, to r ecruit endogenous or exogenous proteinases to mediate proteolysis asso ciated with diapedesis and chemotactism during the inflammation proces s.