Function and Structure of Human Leucocyte Collagenase

Abstract

Human leucocyte collagenase is one member of the growing protein family of matrix metalloproteinases (MMPs) [Knäuper et al., 1990]. It is a calcium-containing Zn-endoproteinase (MMP-8) that cleaves preferentially interstitial native triple-helical type I but also type II and type III collagen into one-quarter and three quarter fragments of the native chain length. If thus differs from the fibroblast interstitial collagenase that preferentially cleaves type III. About one-third of its mass of 65 kDa (for active enzyme) is carbohydrates in contrast to the homologous interstitial collagenase from fibroblasts which carries only a small carbohydrate portion [Tschesche et al., 1992]. The enzyme is stored in the specific granules of granulocytes and is released as a proenzyme, also designated latent enzyme, upon stimulation of the cells by various chemotactic agents, such as formylpeptides, LTB₄, C5a, Fl_a and Zymosan amongst others, [Tschesche et al., 1989 and 1991]. Extracellular activation is then achieved by various different proteinases, such as trypsin, kallikrein, chymotrypsin, cathepsin G [Tschesche et al., 1992] or stromelysin [Knäuper et al., 1993]. However, the physiological process of activation is not yet fully understood, since activation was also observed by isolated leucocyte membranes [Tschesche unpublished].