Lysosomal enzymes collagenase

Osteoclasts are multinucleated cells found on the endosteal surface of bone, in Haversian systems and periosteal surfaces. PTH activates osteoclasts (indirectly via osteoblasts that possess PTH receptors). Calcitonin is a potent inhibitor of osteoclast activity. Local cytokine factors, including interleukin-1 (IL-1), tumour-necrosis factor (TNF), TGF- 0 and interferon-y (INF-y), are important regulators. Osteoclast resorption of bone releases collagen peptides, pyridinoline cross-links and calcium from the bone matrix, through the action of lysosomal enzymes (collagenases and cathepsins). The collagen breakdown products in serum and urine (e.g. hydroxyproline) can be used as biochemical markers. 

An abscess begins by the combined action of inflammatory cells (such as neutrophils), bacteria, fibrin, and other inflammatory mediators. Bacteria may release heparinases that cause local thrombosis and tissue necrosis or fibrinolysins, collagenases, or other enzymes that allow extension of the process into surrounding tissues. Neutrophils gathered in the abscess cavity die in 3 to 5 days, releasing lysosomal enzymes that liquefy the core of the abscess. A mature abscess may have a fibrinous capsule that isolates bacteria and the liquid core from antimicrobials and immunologic defenses. 

The endoglycosidase has a molecular weight of around 80,000 (6, 7). Other lysosomal enzymes are the exoglycosi-dases, the proteases, collagenase, nuclease, sulfatases, and phosphatases. The release of hyaiuronidase from the cancer cell is usually accompanied by a release of increased amounts of other lysosomal enzymes, as has been demonstrated for a wide variety of experimental and human tumors (93, 110, 120, 172, 190, 282, 292, 316). 

As mentioned earlier, it could well be that neoplastic transformation involves an increased and sustained output of all lysosomal enzymes, including collagenase, but there could be a simpler explanation. 

Denatured collagen, as formed post-mortem by the action of lactic acid, can also be cleaved by lysosomal enzymes, e. g., lysosomal collagenase and cysteine proteinase cathepsin Bi. Thermally denatured collagen is attacked by pepsin and trypsin. 

The biochemical properties of chloroquine and related anti-malarials have been exeonined further. In addition to its inhibition of the biosynthesis of sulfated mucopolysaccharides, chloroquine inhibits irreversibly an autolytic enzyme from bovine cartilage and a rat skin collagenase (at 10 mM). Like hydrocortisone, it inhibits chemotaocis of leukocytes and, to a lesser extent, the phagocytosis process.It also stabilizes lysosomal membranes in vitro. Potential "anti-degenerative" activity is clearly suggested by these properties, but unfortunately the well-known retinopathic effect is further complicated by a delayed symptom. 

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