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(American Journal of Pathology. 2002;161:2143-2152.)
© 2002 American Society for Investigative Pathology


Regular Articles

Bacterial Colonization and the Expression of Inducible Nitric Oxide Synthase in Murine Wounds

Eric Mahoney*, Jonathan Reichner*, Leslie Robinson Bostom{dagger}, Balduino Mastrofrancesco*, William Henry* and Jorge Albina*

From the Department of Surgery,* Division of Surgical Research, and the Department of Dermatology,{dagger} Brown Medical School/Rhode Island Hospital, Providence, Rhode Island

The expression of inducible nitric oxide synthase (iNOS) in two different murine wound models was investigated. Animals were subjected to either full-thickness linear skin incision with subcutaneous implantation of sterile polyvinyl alcohol sponges, or to 1.5 x 1.5-cm dorsal skin excision. Reverse transcriptase-polymerase chain reaction detected iNOS mRNA in all cell samples retrieved from the sponges. Immunoblotting of lysates of inflammatory cells harvested from the sponges failed to detect iNOS protein, and immunohistochemistry of the incisional wound was mildly positive. Inflammatory cells of excisional wounds stained strongly positive for iNOS. Cutaneous wounds were found to be colonized with Staphylococcus aureus. The detection of iNOS in cells from sponges inoculated in vivo with heat-killed bacteria and the reduction of immunohistochemical signal for iNOS in excisional wounds of animals treated with antibiotics support a role of bacteria in the induction of iNOS in wounds. The expression of iNOS in excisional wounds requires interferon-{gamma} and functional lymphocytes because interferon-{gamma} knockout and SCID-Beige mice exhibited attenuated iNOS staining in excisional wounds. The expression of iNOS in the inflammatory cells of murine wounds is a response to bacterial colonization and not part of the normal repair process elicited by sterile tissue injury.





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