title: Wound healing in skin promoted by inoculation with Pseudomonas aeruginosa PAO1: The critical role of tumor necrosis factor-α secreted from infiltrating neutrophils.
abstract: Wound healing is promoted by the presence of replicating microorganisms adhering to the wounded tissue, but the precise mechanism is not fully understood. In the present study, using a rat model with full-thickness dermal wounds, we examined the effect of Pseudomonas aeruginosa inoculation on wound healing and the role of neutrophils infiltrating the wound site. Within 3 days, inoculation with this bacterium had accelerated re-epithelialization, epidermal cell proliferation, and neo-vascularization, as well as the local infiltration of neutrophils, which reached a peak at 24 hours. Tumor necrosis factor (TNF)-α was detected in the wound tissues on the mRNA and protein levels within 24 hours. Flow cytometry and immunohistochemical analyses detected higher levels of TNF-α in the infiltrating neutrophils in rats inoculated with P. aeruginosa than in uninoculated rats. Neutropenic rats treated with anti-neutrophil mAb or cyclophosphamide exhibited significant attenuation in re-epithelialization, epidermal cell proliferation, neo-vascularization, and TNF-α synthesis compared with control; administration of TNF-α reversed these attenuations. These wound-healing responses were decelerated in rats treated with anti-TNF-α mAb, as was the infiltration of neutrophils. These results indicate that inoculation with P. aeruginosa promotes wound healing by inducing the infiltration of neutrophils, which play a critical role as a major source of TNF-α.
authors.affiliation: Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Kanno
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.forename: Masae
authors.initials: M
authors.lastname: Ritsu
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishii
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tanno
authors.forename: Sohachi
authors.initials: S
authors.lastname: Toriyabe
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Imai
authors.forename: Ryoko
authors.initials: R
authors.lastname: Maruyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tachi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D020556:Neutrophil Infiltration / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha