We previously reported that leukocyte specific β2 integrins contribute to hypertrophy after muscle overload in mice. Because intercellular adhesion molecule-1 (ICAM-1) is an important ligand for β2 integrins, we examined ICAM-1 expression by murine skeletal muscle cells after muscle overload and its contribution to the ensuing hypertrophic response. Myofibers in control muscles of wild type mice and cultures of skeletal muscle cells (primary and C2C12) did not express ICAM-1. Overload of wild type plantaris muscles caused myofibers and satellite cells/myoblasts to express ICAM-1. Increased expression of ICAM-1 after muscle overload occurred via a β2 integrin independent mechanism as indicated by similar gene and protein expression of ICAM-1 between wild type and β2 integrin deficient (CD18-/-) mice. ICAM-1 contributed to muscle hypertrophy as demonstrated by greater (p<0.05) overload-induced elevations in muscle protein synthesis, mass, total protein, and myofiber size in wild type compared to ICAM-1-/- mice. Furthermore, expression of ICAM-1 altered (p<0.05) the temporal pattern of Pax7 expression, a marker of satellite cells/myoblasts, and regenerating myofiber formation in overloaded muscles. In conclusion, ICAM-1 expression by myofibers and satellite cells/myoblasts after muscle overload could serve as a mechanism by which ICAM-1 promotes hypertrophy by providing a means for cell-to-cell communication with β2 integrin expressing myeloid cells.

Introduction We investigated the extent to which intercellular adhesion molecule-1 (ICAM-1), a critical protein of the inflammatory response, is expressed in skeletal muscles of mdx mice (a murine model of Duchenne muscular dystrophy). Methods Muscles were collected from control and mdx mice at 2–24 weeks of age and analyzed for ICAM-1 expression by means of Western blot and immunofluorescence. Results Western blot revealed higher expression of ICAM-1 in mdx compared with control muscles through 24 weeks of age. In contrast to control muscles, ICAM-1 was expressed on the membrane of damaged, regenerating, and normal myofibers of mdx mice. CD11b+ myeloid cells also expressed ICAM-1 in mdx muscles, and CD11b+ cells were closely associated with the membrane of myofibers expressing ICAM-1. Conclusions These findings support a paradigm in which ICAM-1 and its localization to myofibers in muscles of mdx mice contributes to the dystrophic pathology.

Duchenne muscular dystrophy (DMD) is an X‐linked inherited disease resulting from the absence of the cytoskeletal protein dystrophin in skeletal and cardiac muscle cells. Without dystrophin, skeletal muscles incur repeated cycles of damage and regeneration. In a murine model of DM (i.e. mdx mice), myeloid cells (neutrophils and macrophages) contribute to the onset and progression of DMD. The objective of this investigation was to determine if intercellular adhesion molecule‐1 (ICAM‐1), a protein of the inflammatory response, is expressed by myofibers in mdx mice. We hypothesize that the expression of ICAM‐1 by myofibers in dystrophin‐deficient muscle serves as a mechanism by which myeloid cells exacerbate the muscle pathology. Western blot revealed increased expression of ICAM‐1 in mdx compared to control wild‐type mice. We found ICAM‐1 expressed on the membrane of necrotic, injured, and regenerating myofibers of mdx mice via immunolabeling. Myofibers of control wild‐type mice did not express ICAM‐1. These observations may indicate that skeletal muscle fiber expression of ICAM‐1 serves as a mechanism by which neutrophils and macrophages attach to skeletal muscle and exacerbate the myopathy in the mdx mice.