Role of collagenase in colonic anastomoses: a reappraisal.

Increased collagenolysis, with reduction in collagen concentration, has been incriminated in the breakdown of colonic anastomoses but previous studies have measured only collagen levels and non-specific collagenolytic activity. Collagenase, the initiating enzyme in collagen degradation, is synthesized on demand and controlled by tissue inhibitor of metalloproteinases (TIMP). Antibodies to collagenase and TIMP were applied to colonic anastomoses in rabbits to investigate the role of the enzyme during healing. Within 12 h of operation, secreting cells and extracellular collagenase were identified at the everted edges of the bowel wall. After 24 h, collagenase activity was accompanied by TIMP secretion in the same localized regions, and by the third postoperative day very few cells were still synthesizing enzyme in these areas, although extracellular activity remained visible. TIMP-secreting cells, however, were seen in a layer of connective tissue sealing the serosal surface of the anastomosis. At 7 days, both enzyme and inhibitor were found only in small aggregates of secreting cells in the deeper layers. The localization and extent of collagenase and TIMP activity accorded well with a normal healing response as, at all times, the enzyme was confined to the immediate vicinity of the suture line.