P-selectin inhibition suppresses muscle regeneration following injury.
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 microg/mouse or with 100 microl 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 microg 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.
Baker
Wallace
W
Department of Medical Technology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-0100.
Schneider
Barbara A St Pierre
BA
Kulkarni
Anhurunda
A
Sloan
Gloria
G
Schaub
Robert
R
Sypek
Joseph
J
Cannon
Joseph G
JG
D000818:Animals; D039481:CD11b Antigen / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008297:Male; D051379:Mice; D009132:Muscles / Q000293:injuries / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D013997:Time Factors
D039481:CD11b Antigen; D019007:P-Selectin