Tissue Kallikrein Effectively Activates Latent Matrix Degrading Metalloenzymes

Abstract

Human leukocytes contain a number of phagocytizing cells, e.g. the azurophil granulocytes, which contain various lysosomal proteinases com-partimented in granules. This outfit is used for intracellular breakdown of invading microorganisms incorporated into the phagolysosom, but is also secreted against the extracellular matrix to allow and to facilitate tissue remodeling and matrix barrier penetration^1,2 Besides the serine proteinases elastase and cathepsin G, two metalloproteinases have been demonstrated: Collagenase I cleaving type I, II and III interstitial collagens and colla-genase IV/V-gelatinase directed against type IV and V basement membrane collagens and against gelatin^1-5.Both collagenases are obviously stored and secreted in latent form and require activation to become effective. Activation could be accomplished in vitro by various agents, e.g. mercuri com-pounds, chaotropic agents and proteinases such as trypsin^1,4.5. However, the in vivo pathway and the enzyme(s) involved in in vivo activation remained an open question.