MCP-1 Parallels Inflammatory and Regenerative Responses in Ischemic Muscle

• Published in: The Journal of surgical research 2006-07, Vol.134 (1), p.145-157
• Main Authors: Shireman, Paula K., Contreras-Shannon, Veronica, Reyes-Reyna, Sara M., Robinson, Susan C., McManus, Linda M.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; arteriogenesis; Biological and medical sciences; Chemokine CCL2 - analysis; Chemokine CCL2 - genetics; Chemokine CCL2 - physiology; collateral circulation; Creatine Kinase - metabolism; General aspects; inflammation; Inflammation - etiology; ischemia; Ischemia - physiopathology; L-Lactate Dehydrogenase - metabolism; Leukocyte Count; Male; Medical sciences; Mice; Mice, Inbred C57BL; monocyte chemotactic protein-1; monocyte/macrophage; murine; Muscle, Skeletal - blood supply; Muscle, Skeletal - physiology; neutrophil; Organ Size; Peroxidase - metabolism; Receptors, CCR2; Receptors, Chemokine - physiology; Regeneration; RNA, Messenger - analysis; skeletal muscle regeneration; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2005.12.003

Monocyte chemotactic protein-1 (MCP-1) is important in macrophage recruitment and activation. However, the magnitude and temporal sequence of MCP-1 expression in relation to tissue injury and regeneration following ischemic injury remains unknown. Hind limb ischemia was induced by femoral artery excision (FAE) in C57Bl/6J mice; a sham surgery was performed on the contralateral leg. Muscle lysates were used to measure MCP-1 and activities of creatine kinase, lactate dehydrogenase, and myeloperoxidase. Histology and immunohistochemistry were used to localize inflammation and MCP-1. FAE resulted in a prolonged period of ischemia and the administration of MCP-1 did not alter the restoration of perfusion. One day after femoral artery excision, extensive muscle necrosis and neutrophils were prevalent throughout the musculature of the lower leg. By 3 days, a mononuclear cell infiltrate predominated in association with robust muscle regeneration as indicated by myoD expression. Concomitantly, myeloperoxidase was maximally increased. Muscle enzymes (creatine kinase and lactate dehydrogenase) were maximally decreased within 3 days and returned to baseline levels by day 14, a time course consistent with injury and regeneration observed by histology. In parallel with these inflammatory and regenerative events, MCP-1 in muscle was maximally increased at day 3. By immunohistochemistry, MCP-1 was within vascular endothelial cells and infiltrating macrophages in areas of ischemic injury. The transient increases and selective tissue distribution of MCP-1 during early inflammation and muscle regeneration support the hypothesis that this cytokine participates in the early reparative events preceding the restoration of vascular perfusion following ischemic injury.