P-selectin inhibition suppresses muscle regeneration following injury

Journal of Leukocyte Biology

Barbara A. St. Pierre Schneider³  Robert Schaub¹  Wallace Baker³  Joseph G. Cannon²  Anhurunda Kulkarni³  Gloria Sloan²  Joseph Sypek¹ 

[1] Wyeth Research, Andover, Massachusetts Wyeth Research, Andover, Massachusetts Wyeth Research, Andover, MassachusettsDepartments of Medical Technology and Physiology, Medical College of Georgia, Augusta; Departments of Medical Technology and Physiology, Medical College of Georgia, Augusta; Departments of Medical Technology and Physiology, Medical College of Georgia, Augusta;;Noll Physiological Research Center, Pennsylvania State University, University Park; and Noll Physiological Research Center, Pennsylvania State University, University Park; and Noll Physiological Research Center, Pennsylvania State University, University Park; and

关键词: macrophage;    satellite cell;    dendritic cell;    myotube;   

DOI  :  10.1189/jlb.1102528

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

This investigation sought to determine if P-selectin-mediated mechanisms contributed to macrophage localization in damaged muscle, an essential process for muscle regeneration. Mice were injected intravenously (i.v.) with soluble P-selectin glycoprotein ligand-1 (sPSGL-1) at 5, 50, or 200 μg/mouse or with 100 μl vehicle alone, and then, lengthening contractions were induced in hindlimb plantar-flexor muscles. The contractions caused fiber damage in soleus muscles, with maximal invasion by CD11b+ mononuclear cells at 24 h post-injury and substantial accumulation of CD11b+ mononuclear cells in the extracellular matrix up to 7 days post-injury. sPSGL-1 treatment caused a dose-dependent decrease in the number of regenerating fibers (P=0.021), as determined by developmental myosin heavy chain (dMHC) expression. This expression was reduced 93% at 7 days post-injury by the highest dose of sPSGL-1, which had no significant influence on intrafiber or extracellular accumulation of cells expressing CD11b, a general marker for phagocytic cells. Additional mice were injected i.v. with 20 μg anti-P-selectin or isotype-control immunoglobulin G and were then subjected to lengthening contractions as before. At 7 days post-injury, soleus muscles from anti-P-selectin-treated mice contained 48% fewer mononuclear cells that bound ER-BMDM1 (P=0.019), a marker for mature macrophages and dendritic cells, and 84% fewer fibers expressing dMHC (P = 0.006), compared with muscles from isotype-injected, control mice. The number of CD11b+ cells was not significantly different between groups. The results are consistent with the concept that P-selectin is involved in the recruitment, maturation, and/or activation of cells that are critical for muscle fiber regeneration.

【 授权许可】

Unknown