LOCALIZATION OF MESSENGER-RNAS REPRESENTING COLLAGENASE AND TIMP IN SECTIONS OF HEALING HUMAN BURN WOUNDS

Interstitial collagenase, a matrix metalloproteinase, is known to be a ctively involved in remodeling of cutaneous tissues including those af fected by trauma, neoplasia, and inflammation. Conversely, collagenase activity is blocked by tissue inhibitor of metalloproteinases (TIMP). Because both collagenase and TIMP are rapidly secreted into the extra cellular matrix, their sites of synthesis remain ambiguous. To determi ne the site and sequence of collagenase and TIMP expression in cutaneo us wound repair, we examined partial and full thickness excisions of h uman burn wounds representing days 2 to 34 postinjury. Prominent label ing for collagenase and TIMP was detected in epithelial cells at the b urn margin and at the edges of surviving hair follicles and eccrine sw eat structures in the wound bed. Within the dermis, cells expressing c ollagenase and TIMP were at first perivascular in location and later a ppeared at the interface zone between viable and nonviable dermis. A d iversity of cell types including macrophages, fibroblasts, endothelial cells, and keratinocytes appeared to express mRNAs for collagenase an d TIMP. Little if any labeling was detected in necrotic regions, in ad jacent nonwounded dermis, or epidermis. Our data indicate that collage nase and TIMP are temporally and spatially regulated during cutaneous wound repair.