Ad. Pemberton et al., DIFFERENTIAL INHIBITION OF MAST-CELL CHYMASES BY SECRETORY LEUKOCYTE PROTEASE INHIBITOR, Biochimica et biophysica acta (G). General subjects, 1379(1), 1998, pp. 29-34
The major physiological role of human secretory leukocyte protease inh
ibitor (SLPI), a low molecular weight inhibitor present in mucus, is t
he rapid formation of a tight-binding inhibitory complex with neutroph
il elastase. It is also the most effective known inhibitor of human ma
st cell chymase. The inhibitory efficacy of recombinant SLPI towards t
hree other mast cell chymases was therefore investigated. Rat mast cel
l proteinases-l and -2 (rMCP-1 and -2, respectively) and sheep mast ce
ll proteinase-1 (sMCP-1), a chymase with additional tryptase-like prop
erties, were treated with the inhibitor. SLPI inhibited rMCP-1 very ef
ficiently in the absence of heparin, with a low dissociation constant,
K-i = 3 x 10(-10) M and high second order association constant, k(ass
) = 8.0 x 10(6) M-1 s(-1), and inhibition was enhanced when heparin wa
s present. rMCP-2 was not inhibited by SLPI in the presence or absence
of heparin, and did not degrade SLPI on prolonged incubation. SLPI in
hibited sMCP-1 very poorly in the absence of heparin (K-i = 9 x 10(-6)
M). However, in the presence of heparin, the K-i for inhibition of sM
CP-1 by SLPI was reduced to the nanomolar range. sMCP-1 was observed t
o cleave SLPI with chymase-like specificity at Leu(72)-Met(73) on prol
onged incubation in the absence of heparin, but increasing concentrati
ons of heparin reduced the extent of cleavage. (C) 1998 Elsevier Scien
ce B.V.