title: Bacterial colonization and the expression of inducible nitric oxide synthase in murine wounds.
abstract: 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.
authors.affiliation: Department of Surgery, Division of Surgical Research, Brown Medical School/Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Mahoney
authors.forename: Jonathan
authors.initials: J
authors.lastname: Reichner
authors.forename: Leslie Robinson
authors.initials: LR
authors.lastname: Bostom
authors.forename: Balduino
authors.initials: B
authors.lastname: Mastrofrancesco
authors.forename: William
authors.initials: W
authors.lastname: Henry
authors.forename: Jorge
authors.initials: J
authors.lastname: Albina
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012867:Skin / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development*; D015503:Surgical Sponges; D014945:Wound Healing; D014946:Wound Infection / Q000201:enzymology / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse