P-selectin inhibition suppresses muscle regeneration following injury

被引:11
作者
Baker, W
Schneider, BAS
Kulkarni, A
Sloan, G
Schaub, R
Sypek, J
Cannon, JG
机构
[1] Med Coll Georgia, Sch Allied Hlth Sci, Dept Med Technol, Augusta, GA 30912 USA
[2] Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA
[3] Penn State Univ, Noll Physiol Res Ctr, University Pk, PA 16802 USA
[4] Wyeth Ayerst Res, Andover, MA USA
关键词
macrophage; satellite cell; dendritic cell; myotube;
D O I
10.1189/jlb.1102528
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
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 mug/mouse or with 100 mul 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 mug 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 hound 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.
引用
收藏
页码:352 / 358
页数:7
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