Collagenase production

Adhesion molecule expression, inflammatory cell activation and chemotaxis, fibroblast proliferation and collagenase production, endothelial cell proliferation, increases BHR ... 

Initial studies with mast cell cultures or granules demonstrated that mast cells appear to have several important effects on connective tissue elements. Subba Rao et al. (1983) showed that cultured rat embryonic skin fibroblasts phagocytose rat mast cell granules added to the culture medium or released by co-culmred mast cells, and that this is followed by secretion of collagenase and p-hexosaminidase. Similarly Yoffe et al. (1984) demonstrated that granules derived from mast cells purified from dog mastocytomas induced a 10- to 50-fold stimulation of collagenase production by human... 

B6. Balavoine, J. F., de Rochemonteix, B., Williamson, K., Seckinger, P., Cruchaud, A., and Dayer, J. M. Prostaglandin E2 and collagenase production by fibroblasts and synovial cells is regulated by urine-derived human interleukin-1 and inhibitor(s). 7. Clin. Invest. 78, 1120-1124 (1986). 

Collagenase production and release are partly responsible for the joint destruction that characterises human rheumatoid arthritis. Triterpenes from the lupane and a-amyrin groups have been studied in vitro to examine their effects on the release of the arthritic joint degradative enzyme collagenase using the rat osteosarcoma. This test and the rat synovial granuloma of adjuvant arthritis are similar both models are based on connective tissue tumours with bone-invasive properties. The pentacyclic triterpenes assayed have been shown to possess general antiproteolytic effects that can explain the anti-arthritic effects in adjuvant arthritis in rats [71,103]. 

The authors demonstrated that the enzyme is produced by viable ceils during culture by (1) failure of collagenase production by cultured tissues previously killed by repeated freezing and thawing, and (2) failure of collagenase production in cultured viable tissues incubated with puromycin, an antibiotic which inhibits protein synthesis. 

Eisen and Gross (1965) sought to determine the tissue source of eol-lagenase and hyaluronidase as well as the role of these enzymes in tadpole tail resorption. Epithelium was separated from connective tissues of the tail fins with the aid of an elastase digestion, and the tissues were tested separately for collagenase production, Collagenase was detected only in culture fluids of epithelial cells. Hyaluronidase could be detected in either the culture fluids or in homogenates of the mesenchymal tissues (Silbert et al, 1965). 

The rheumatoid tissues varied histologically from highly vascular tissues which were intensely infiltrated with inflammatory cells to those that displayed scant ccllularity. The authors made an attempt to correlate the severity of various features of inflammation with collagenase production. High coUagenoIytic activity was particularly related to proliferation of vascular tissues. 

Hasty, K. A., Pourmotabbed, T. F., Goldberg, G. I., Thompson, J. P., Spinella, D. G., Stevens, R. M., Mainardi, C. L. (1990). Human neutrophil collagenase A distinct gene product with homology to other matrix metalloproteinases. J. Biol. Chem. 265,... 

Interstitial collagenases catalyze the degradation of types I, II, and III collagen. Cleavage occurs at a single site, approximately of the distance from the carboxy-terminal end. The f and degradation products are unstable and are further broken down by either the same collagenases or other proteases. The initial bond cleaved is either a Gly-Leu or a Gly-Ile. 

Finally, fibroblasts respond to chemotoxins derived from other cells, macrophages and lymphocytes, that could increase fibrous protein production or collagenase activity. For example, some fibrotic lungs show a 2.5-fold increase in collagen (Madri and Furthmayr, 1980). 

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