Selective Neutrophil Depletion with Monoclonal Antibodies Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle

Abstract

The purpose of this study was to determine whether depletion of circulating neutrophils, using an antineutrophil monoclonal antibody (RP3), would attenuate ischemia/reperfusion injury in rat skeletal muscle. A 3- and 5-hr period of ischemia was induced unilaterally into the hindlimbs of rats; the isolated limbs were then reperfused for 24 hr after ischemia. The gastrocnemius muscle was then removed, and blood was taken simultaneously. The hematologic parameters were measured, muscle neutrophil sequestration was assessed by myeloperoxidase (MPO) activity, free radical production was evaluated by the tissue lipid peroxides (LPO) levels, muscle viability was assessed by tissue levels of adenosine triphosphate (ATP) and creatine phosphate (PCr) levels, and muscle wet/dry weights were determined. Treatment with RP3 selectively and sufficiently depleted the circulating neutrophil population, markedly reduced MPO, and significantly attenuated LPO and the tissue water content after both 3- and 5-hr of ischemia. After 3 hr of ischemia, ATP and PCr levels were significantly increased by neutrophil depletion; however, after 5 hr of ischemia, the same effect was not demonstrated. These results suggest that neutrophil depletion after 3 hr of ischemia restrains free radical production and edema formation, and also attenuates skeletal muscle ischemia reperfusion injury; however, after 5 hr of ischemia, ischemic damage was so severe, that neutrophil depletion did not reduce ischemia reperfusion injury.

Neutrophil-induced skeletal muscle damage: a calculated and controlled response following hindlimb unloading and reloading

“…Recent results from our laboratory and others have shown that leukocyte recruitment in skeletal muscle varies in number and type, depending on the insult (19,28,34,46,51,52). However, there is no correlation between the number of neutrophils and the extent of collateral muscle damage.…”

N-acetylcysteine Protects Striated Muscle in a Model of Compartment Syndrome

“…Acute respiratory distress syndrome, multiorgan failure, and death have been described as consequences of IRI [7,15]. Neutrophil activation and infiltration have been identified as primary protagonists in the pathophysiology of IRI [10,21,22]. CS results in a much greater level of metabolic strain and cellular deterioration than IRI alone, and its treatment is urgent surgical decompression by fasciotomy once identified [18,19,37,40,49].…”

Inflammation et régénération musculaire

“…Ainsi, dans un modèle de blessure musculaire induite par une toxine ou une infection, la suppression des neutrophiles entraîne la persistance des fibres nécrotiques [12]. La forte capacité catabolique des neutrophiles a cependant été associée égale-ment à l'induction de dommages collatéraux observés à la suite du recrutement massif de ces cellules induit par ischémie-reperfusion du tissu musculaire [13]. Les effets positifs ou négatifs des neutrophiles sur la régénération tissulaire dépendraient de leur degré d'activation qui varie selon le type et la gravité de la inflammatoire stérile (en absence d'agents infectieux) se caractérise par l'activation rapide de cellules sentinelles, suivie d'une infiltration massive et de courte durée de neutrophiles et, finalement, du recrutement de monocytes qui se différencient en macrophages [6].…”