Estrogen modulates 7/4 antigen distribution within eccentrically contracted injured skeletal muscle.

Eccentric contractions are skeletal muscle stretches with concurrent active force production; these contractions commonly occur during dynamic sports activities and can cause acute muscle injury. Recovery from this injury depends in part on pro-inflammatory processes, such as neutrophil infiltration at the injured site, which is affected by estrogen. This estrogen effect has been examined broadly, but without distinguishing between major compartments within muscle in which neutrophil infiltration can occur. Therefore, we compared neutrophil antigen expression in two compartments of eccentrically contracted muscle of ovariectomized mice with or without estrogen. To quantify neutrophil antigen expression, serial cross sections of muscle were immunolabeled with antibodies that recognize 7/4 or Ly6C/G, then quantified using computer-assisted image analysis. At 48 h post injury, estrogen-positive (E+) mice had more 7/4-positive and Ly6C/G-positive myofibers, increased 7/4 area percentage, and more 7/4-positive cells in the connective tissue. In addition, E+ mice showed more 7/4-positive myofibers that were Ly6C/G-negative and more Ly6C/G-positive myofibers that were 7/4-negative. These data suggest that in injured muscle, estrogen increases 7/4 antigen in connective tissue and myofibers and is associated with more Ly6C/G-positive myofibers when the 7/4 antigen is absent from these myofibers.

M1/70 attenuates blood-borne neutrophil oxidants, activation, and myofiber damage following stretch injury.

The purpose of this study was to determine the role of the CD11b-dependent respiratory burst in neutrophil oxidant generation and activation, interleukin-8 (IL-8) production, and myofiber damage after muscle stretch injury by using the monoclonal antibody M1/70 to block this pathway. Twelve male New Zealand White rabbits were randomly assigned to a treatment group: M1/70 (n = 6), IgG isotype control (n = 3), or saline control (n = 3). After intravenous injection of the assigned agent under gas anesthesia, a standardized single-stretch injury was created in the right tibialis anterior, whereas the left tibialis anterior underwent a sham surgery. Blood-borne neutrophil oxidant generation and CD11b receptor density and plasma IL-8 levels were measured pre- and 24 h postinjury. Damage was assessed histologically at the hematoma site by counting torn myofibers. M1/70 group demonstrated decreased blood-borne neutrophil oxidant generation (P < 0.05) and CD11b receptor density (P < 0.05), an increase in plasma IL-8 concentration (P < 0.01), and less torn myofibers (P < 0.01) compared with IgG isotype or saline control groups. These data indicate that 1). CD11b-dependent respiratory burst is a major source of oxidants produced by the neutrophil, and that treatment with M1/70 2). attenuates neutrophil activation status, 3). increases plasma IL-8 concentration, and 4). minimizes myofiber damage 24 h postmuscle stretch injury.

Sex differences in leukocyte invasion in injured murine skeletal muscle.

The three aims of this study were to describe the time course of leukocyte invasion in injured soleus muscles of male and female mice, to determine if differential subsets of leukocytes accumulate in intramyofiber and interstitial sites, and to determine if significant sex differences exist in invading leukocyte concentrations. Fifty sexually mature C57BL/6J mice (aged 11-12 weeks) underwent unilateral hindlimb muscle injury induced by lengthening contractions. This procedure models the muscle injury that can occur through strenuous exercise or overuse in humans. After 1, 3, 5, or 7 days of recovery, the injured and contralateral, uninjured solei were dissected and prepared for morphologic analysis. We found that leukocytes had invaded injured myofibers at 1-day postinjury for both sexes. Different subsets of leukocytes accumulated within damaged myofibers and the interstitium. Significantly fewer myofibers were invaded by acid phosphatase-positive leukocytes in females. Interstitial ER-BMDM1 leukocyte concentrations peaked in females at 7 days postinjury in comparison to 5 days postinjury in males. These findings expand nursing's knowledge base regarding the potential effect of gender on recovery from acute muscle injury.

Association of IGF-I and IGF-II with myofiber regeneration in vivo.

This study examined expression of insulinlike growth factor (IGF) in the myofibers and nonmyofibrillar structures of murine soleus muscle following contraction-induced damage. Identifying the cellular sources of this myogenic growth factor could improve muscle rehabilitation strategies. Immunohistochemical analysis of muscle sections indicated that the number of myofibers expressing both IGF-I and IGF-II increased significantly at 4, 7, and 10 days following injury, compared with control. Muscle spindles and vascular tissue expressed only IGF-II, and staining intensity did not change following injury. The number of fibers expressing developmental myosin heavy chain increased significantly at 7 and 10 days postinjury, and these usually coexpressed IGF. No IGF-specific staining of interstitial/inflammatory cells was observed. Therefore, expression of IGF after mechanically induced fiber damage occurs exclusively within regenerating fibers without supplemental delivery of IGF to the tissue by inflammatory cells or changes in constitutive expression of IGF-II in vascular tissue.