title: The loss of MCP-1 attenuates cutaneous ischemia-reperfusion injury in a mouse model of pressure ulcer.
abstract: The formation of pressure ulcers is dependent on multiple factors including ischemia-reperfusion (IR). This study assessed the mechanism of a previously reported murine model of cutaneous IR injury. Three cycles of IR (days 1-3) by external application of two magnetic plates were performed to induce pressure ulcer formation. Increased infiltration of neutrophils and macrophages, and augmented expression of proinflammatory cytokines and inducible nitric oxide synthase (iNOS), were observed during IR cycles. In this model, monocyte chemoattractant protein-1 (MCP-1) was remarkably increased at day 1 in the skin followed by inflammatory cell infiltration. Therefore, IR cycles were performed in MCP-1-deficient (MCP-1(-/-)) mice to evaluate the role of this chemokine in pressure ulcer development. MCP-1(-/-) mice showed reduced macrophage infiltration and expression of tumor-necrosis factor-alpha (TNF)-alpha and iNOS during IR cycles leading to attenuated apoptosis and skin injury. Importantly, MCP-1 played a role in apoptosis and injury via inducing iNOS during the reperfusion rather than the ischemic period. These findings indicate that MCP-1 may be a critical factor for macrophage recruitment and subsequent skin inflammation and injury during IR cycles. We propose that this is a useful model for investigating the mechanism of pressure ulcer formation using various transgenic mice.
authors.affiliation: Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Mayuka
authors.initials: M
authors.lastname: Horikawa
authors.forename: Motoi
authors.initials: M
authors.lastname: Takenaka
authors.forename: Fumihide
authors.initials: F
authors.lastname: Ogawa
authors.forename: Junko
authors.initials: J
authors.lastname: Sugama
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
mesh_terms: D000818:Animals; D017209:Apoptosis; D018932:Chemokine CCL2 / Q000097:blood / Q000502:physiology*; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D003668:Pressure Ulcer / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D014945:Wound Healing
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II