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.