Expression of inducible nitric oxide synthase in human burn wounds

Nitric oxide is produced by various cell types and can initiate either beneficial or deleterious effects. Because cultured human keratinocytes express an inducible isoform of nitric oxide synthase, it was postulated that keratinocytes within a burn wound would express increased levels of inducible nitric oxide synthase following the injury. Immunohistochemical staining identified the sites of cellular expression and temporal sequence of inducible nitric oxide synthase protein within partial- and full-thickness burns excised from 29 patients. While migrating keratinocytes at the immediate edge of the wounds showed decreased or undetectable levels of inducible nitric oxide synthase, the immediately adjacent proliferative population and upwardly growing keratinocytes from surviving hair follicles showed increasingly greater cytoplasmic staining for inducible nitric oxide synthase at 4-21 days after injury. Noninjured skin showed minimal inducible nitric oxide synthase staining. Within the wound, detectable inducible nitric oxide synthase protein appeared to decrease as keratinocytes assumed a differentiated phenotype in the outer newly resurfaced epidermis, in inner root sheath layers of hair follicles, or in epithelium of eccrine sweat ducts. Within granulation tissue, immunoreactive inducible nitric oxide synthase was detected in capillary endothelium and in arterial smooth muscle layer. Focal increases in inducible nitric oxide synthase expression were noted in association with inflammatory infiltrates. In conclusion, the cellular and temporal distributions of immunoreactive inducible nitric oxide synthase suggest that nitric oxide may play a role in the regulation of wound repair processes beyond the acute burn injury.