Expression of thrombomodulin and consequences of thrombomodulin deficiencyduring healing of cutaneous wounds

Thrombomodulin is a cell surface anticoagulant that is expressed by endothe lial cells and epidermal keratinocytes. Using immunohistochemistry, we exam ined thrombomodulin expression during healing of partial-thickness wounds i n human skin and full-thickness wounds in mouse skin, We also examined thro mbomodulin expression and wound healing in heterozygous thrombomodulin-defi cient mice, compound heterozygous mice that have <1% of normal thrombomodul in anticoagulant activity, and chimeric mice derived from homozygous thromb omodulin-deficient embryonic stem cells. In both human and murine wounds, t hrombomodulin was absent in keratinocytes at the leading edge of the neoepi dermis, but it was expressed strongly by stratifying keratinocytes within t he neoepidermis. No differences in rate or extent of reepithelialization we re observed between wild-type and thrombomodulin-deficient mice. In chimeri c mice, both thrombomodulin-positive and thrombomodulin-negative keratinocy tes were detected within the neoepidermis. Compared with wild-type mice, he terozygous and compound heterozygous thrombomodulin-deficient mice exhibite d foci of increased collagen deposition in the wound matrix. These findings demonstrate that expression of thrombomodulin in keratinocytes is regulate d during cutaneous wound healing. Severe deficiency of thrombomodulin antic oagulant activity does not appear to alter reepithelialization but may infl uence collagen production by fibroblasts in the wound matrix.