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

Abstract

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.

Neutrophils contribute to muscle injury and impair its resolution after lengthening contractions in mice

“…The observation that CD18−/− mice are protected from contraction-induced muscle injury and oxidative damage in the present study are in agreement with Brickson et al (2003) who reported that the administration of a blocking antibody for neutrophils reduced histological signs of muscle injury in rabbits 24 h after a single lengthening contraction. On the other hand, Lowe et al (1995) reported that neutrophils do not cause muscle injury after lengthening contractions based on observations made after administering a blocking antibody for neutrophils.…”

Regulatory interactions between muscle and the immune system during muscle regeneration

“…For example, muscle injury following a puncture wound with a needle was reduced by administration of functionblocking, soluble CD11b or antibodies to CD11b prior to needle puncture, and the reduced injury was accompanied by a reduction in neutrophils entering the damaged tissue (138). Similarly, systemic administration of function-blocking, antiCD11b before applying mechanical injury to muscle was sufficient to reduce muscle fiber damage (10). Thus, reductions of central nucleation in muscle fibers following injury of phagocyte-depleted mice may reflect both reductions in phagocyte-mediated damage and impaired regenerative capacity caused by slower removal of cellular debris.…”

Degenerative and regenerative features of myofibers differ among skeletal muscles in a murine model of muscular dystrophy

“…Neutrophils are the first inflammatory cells to infiltrate the injured muscle, with a significant increase in their numbers as early as 1-6 h after myotoxin-or exercise-induced muscle damage (Orimo et al 1991;Fielding et al 1993). Some reports revealed that prevention of neutrophil infiltration after injury reduces force deficits and histological damage to muscle fibers (Walden et al 1990;Brickson et al 2003;Pizza et al 2005;Lockhart and Brooks 2008), suggesting that neutrophils contribute to muscle fiber damage. In the present study, although neutrophils did not show a correlation with degenerating myofibers, a negative correlation with regenerated myofibers was noted, indicating that neutrophils decrease with progression of regeneration.…”