Poster abstracts
Poster number 24 submitted by Zachary Howard
Early Tissue-Specific Variations in Resident and Infiltrating Myeloid Populations Contained in mdx Skeletal Muscle
Zachary Howard (OSBP), Jeovanne Lowe (Physiology and Cell Biology; OSU), Dr. Shyam S. Bansal (Physiology and Cell Biology; OSU), Dr. Jill A. Rafael-Fortney (Physiology and Cell Biology; OSU)
Abstract:
Duchenne muscular dystrophy (DMD) is a hereditary, fatal disease affecting males that is characterized by progressive skeletal muscle degeneration and cardiomyopathy. Current treatment options are limited; respiratory complications and heart failure are the leading causes of death during the third decade of life. Loss of function mutations of dystrophin, a large structural protein localized to the sarcolemma that mitigates contractile stress, renders myocytes susceptible to contraction-induced injury. Within skeletal muscle, perpetual cycles of muscle degeneration and regeneration are influenced by chronic inflammation and the continual deposition of connective tissue in lieu of muscle. While the development of fibrosis is a known cause of pathology in dystrophic patients, contributions of dysregulated inflammation to the induction and development of fibrosis in skeletal muscle are largely unknown. Variations in pathology between individual skeletal muscles may in part be explained by the divergent evolution and distinct regulation of resident and infiltrating immune cells unique to those tissues. Embryonic-derived resident and monocyte-derived invasive macrophages in other diseases have contrasting functions, the latter operating as pro-inflammatory while the former contributing to regeneration. Utilizing the mdx mouse and advanced flow cytometric analyses adapted from other fields, our laboratory has begun identifying and functionally characterizing differences in distinct and continuous myeloid populations contained in 4-week old mdx quadriceps and diaphragms. Using a combination of cell-surface markers that identify infiltrating, phagocytic and antigen-presenting myeloid cells, we have detected differences in various population percentages of CD45 positive cells and total cell number between 4-week old mdx quadriceps and diaphragms. Organizational differences in early resident and invading leukocyte populations between mdx skeletal muscles are likely accompanied by alterations in inflammatory signaling. Temporal analysis is necessary to determine the consequences on pathology and provide a more thorough understanding of skeletal muscle immunology that may contribute to chronic muscle diseases.
Keywords: Duchenne, Inflammation, Muscle