INTERACTIONS OF GELATINASES WITH SOLUBLE AND IMMOBILIZED FETUIN AND ASIALOFETUIN

We have analyzed the interactions of human and mouse gelatinases with fetuin and asialofetuin. The data showed that recombinant human gelati nase A (MMP-2) and B (MMP-9) were both specifically bound to asialofet uin and fetuin immobilized to activated agarose (affigel) with subsequ ent cleavage of the enzymes to lower molecular weight forms, which wer e likewise bound to asialofetuin/fetuin. The binding of gelatinases to immobilized forms of asialofetuin and fetuins was abrogated in the pr esence of either soluble fetuin or asialofetnin. Endogenous mouse macr ophage gelatinases (mol wt 92 and similar to 52 kDa) were also specifi cally bound to immobilized asialofetuin upon which the two forms of th e gelatinases were reduced to a similar to 45-kDa fragment. The bindin g of the similar to 45-kDa fragment to asialofetuin was also abrogated in the presence of either soluble fetuin or asialofetuin. Whereas onl y the activated MMP-2 bound to immobilized asialofetuin had significan t gelatinolytic activity, both the zymogen and the activated forms of MMP-9 hydrolyzed soluble [H-8]gelatin to the same extent while still b ound to asiaIofetuin. Our data suggest that cell surface bound fetuin/ asialofetuin could perform two functions: they could (a) act as cell s urface receptors or anchors for MMP-2 and MMP-9 and (b) bind and activ ate MMP-9 on the cell surface. (C) 1995 Academic Press, Inc.