ANTIBACTERIAL ACTIVITY OF ANTILEUKOPROTEASE

Antileukoprotease (ALP), or secretory leukocyte proteinase inhibitor, is an endogenous inhibitor of serine proteinases that is present in va rious external secretions. ALP, one of the major inhibitors of serine proteinases present in the human lung, is a potent reversible inhibito r of elastase and, to a lesser extent, of cathespin G. In equine neutr ophils, an antimicrobial polypeptide that has some of the characterist ics of ALP has been identified (M. A. Couto, S. S. L. Harwig, J. S. Cu llor, J. P. Hughes, and R. I. Lehrer, Infect. Immun. 60:5042-5047, 199 2). This report, together with the cationic nature of ALP, led us to i nvestigate the antimicrobial activity of ALP. ALP was shown to display marked in vitro antibacterial activity against Escherichia coli and S taphylococcus aureus. On a molar basis, the activity of ALP was lower than that of two other cationic antimicrobial polypeptides, lysozyme a nd defensin. ALP comprises two homologous domains: its proteinase-inhi bitory activities are known to be located in the second COOH-terminal domain, and the function of its first NH2-terminal domain is largely u nknown. Incubation of intact ALP or its isolated first domain with E. coli or S. aureus resulted in killing of these bacteria, whereas its s econd domain displayed very little antibacterial activity. Together th ese data suggest a putative antimicrobial role for the first domain of ALP and indicate that its antimicrobial activity may equip ALP to con tribute to host defense against infection.