ACTIVATION OF PRECURSORS FOR MATRIX METALLOPROTEINASE-1 (INTERSTITIALCOLLAGENASE) AND METALLOPROTEINASE-3 (STROMELYSIN) BY RAT MAST-CELL PROTEINASE-I AND PROTEINASE-II

Histological studies have previously demonstrated an association betwe en mast-cell activation/degranulation and areas of connective-tissue l ysis in vivo; in addition, mast-cell extracts have been shown to activ ate latent forms of collagenase and stromelysin. In the present study we have examined the potential roles of rat mast-cell proteinase (RMCP ) I and RMCP II as activators of the precursors of matrix metalloprote inase (MMP)-1 (interstitial collagenase), MMP-2 (gelatinase A) and MMP -3 (stromelysin 1). Both RMCPs I and II activated proMMP-3 by converti ng the 57 kDa precursor into a 45 kDa polypeptide. The N-terminal amin o acid of 45 kDa MMP-3 activated by RMCP II was identified as Phe(83). By contrast, only RMCP II activated the 52 kDa proMMP-1 by converting it into a 41 kDa protein and generating the new N-termini, namely Gln (80) and Val(82). The collagenolytic activity which resulted from this cleavage was only 35% of the full activity, but this could not be aug mented by subsequent treatment with MMP-3, the latter being a crucial enzyme for the generation of the fully active MMP-1 with Phe(81) at th e N-terminus, in conjunction with other serine proteinases. Thus RMCP II activates proMMP-1 via a mechanism different from that reported for the stepwise processing by combinations of other trypsin-like enzymes and MMP-3. ProMMP-2 (progelatinase A) was not activated by either RMC P I or RMCP II, despite processing to smaller products.