Inactivation of human plasma α₁‐proteinase inhibitor by human PMN leucocyte collagenase

Abstract

Highly purified human polymorphonuclear leucocyte collagenase cleaved human e-l-proteinase inhibitor (~I-PI) at the carboxyl site of Phe asz (PT). The inhibitor was thereby rapidly inactivated and generated a primary degradation product as shown by reverse-phase HPLC and N-terminal sequencing. Prolonged incubation of the modified inhibitor with polymorphonuclear leucocyte collagenase led to the generation of a secondary degradation product with additional cleavage at the carboxyl site of Pro 3s7 (Pz).

Degradation of cartilage aggrecan by collagenase‐3 (MMP‐13)

“…MMP-7 [42] and MMP-8 [43] have also been shown to cleave between proline and methionine residues. The cleavage at P384-V385 in aggrecan is clearly a minor activity of MMP-13 since high enzyme concentrations are required for cleavage at this site to occur.…”

Fragmentation of human polymorphonuclear-leucocyte collagenase

“…Transfected Chinesehamster ovary cells containing the cDNA encoding human TIMP-2 were used for the isolation of rTIMP-2 as recently published (DeClerck et al, 1991 (Knauper et al, 1990b. The inactivation of x2-antiplasmin was demonstrated by monitoring the residual inhibitory activity with human plasmin as target proteinase.…”

“…The active PMNL collagenase and the Mr,40000 fragment share the ability to cleave the synthetic octapeptide, gelatin and certain members of the serpin superfamily, such as a,-proteinase inhibitor, Cl-inhibitor or a2-antiplasmin (Knauper et al, 1990bMichaelis et al, 1990;Desrochers et al, 1992). This is obviously an intrinsic property of the catalytic domain.…”

Proteolytic inactivation of human α1 antitrypsin by human stromelysin

“…Furthcrmorc, whilst the printary site BFLTIAT cleavngc by human Rcutrophil collagenase is F%P-LeP (F+Pb), a secondary clcavagc at Pro'"7-Met"n occurs after prolonged incubation [3]. MOW?…”

“…Recently, however, it has been shown that human neutrophil collagenase, a metalloproteinase, is capable of inactivating human (uIAT by catalytic cleavage at the Phe352-Leu353 peptide bond [3,4]. It was therefore suggested that collagenase may contribute to the persisting activity of ncutrophil elastase.…”