TY - JOUR
T1 - The loss of MCP-1 attenuates cutaneous ischemia-reperfusion injury in a mouse model of pressure ulcer
AU - Saito, Yuki
AU - Hasegawa, Minoru
AU - Fujimoto, Manabu
AU - Matsushita, Takashi
AU - Horikawa, Mayuka
AU - Takenaka, Motoi
AU - Ogawa, Fumihide
AU - Sugama, Junko
AU - Steeber, Douglas A.
AU - Sato, Shinichi
AU - Takehara, Kazuhiko
N1 - Funding Information:
We thank Ms M Matsubara and Y Yamada for technical assistance. This work was supported by a grant-in-aid from the Ministry of Education, Science, and Culture of Japan (to M Hasegawa, S Sato, and K Takehara).
PY - 2008/7
Y1 - 2008/7
N2 - 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-α (TNF)-α 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.
AB - 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-α (TNF)-α 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.
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U2 - 10.1038/sj.jid.5701258
DO - 10.1038/sj.jid.5701258
M3 - Article
C2 - 18219277
AN - SCOPUS:45349086431
SN - 0022-202X
VL - 128
SP - 1838
EP - 1851
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 7
ER -