Local tissue damage induced by crotaline
snake venoms includes
edema, myonecrosis,
hemorrhage, and an inflammatory response associated with a prominent cellular infiltrate. The role of neutrophils in the local tissue damage induced by Bothrops asper
snake venom and by
myotoxin I, a
phospholipase A2 isolated from this
venom, was investigated. Male Swiss mice were pretreated with either an antimouse granulocyte rat monoclonal
immunoglobulin G (
IgG) antibody or with isotype-matched control antibody. No significant differences in these local effects were observed between mice pretreated with antigranulocyte
antibodies and those receiving control
IgG. Moreover,
myotoxicity induced by B. asper
myotoxin I was similar in neutrophil-depleted and control mice. The role of neutrophils in the process of skeletal muscle regeneration was also assessed. Muscle regeneration was assessed by quantifying the muscle levels of
creatine kinase and by morphometric histological analysis of the area comprised by regenerating cells in damaged regions of skeletal muscle. Mice depleted of neutrophils and then injected with B. asper
venom showed a more deficient regenerative response than mice pretreated with control
IgG. Moreover, a drastic difference in the regenerative response was observed in mice injected with
myotoxin I, because animals pretreated with control
IgG showed a successful regeneration, whereas those depleted of neutrophils had abundant areas of necrotic tissue that had not been removed 7 days after injection, associated with reduced contents of
creatine kinase. It is concluded that (1) neutrophils do not play a significant role in the acute local pathological alterations induced by the
venom of B. asper, and (2) neutrophils play a prominent role in the process of skeletal muscle regeneration after injection of B. asper
venom and
myotoxin I, probably related to the phagocytosis of necrotic material and the recruitment of other inflammatory cells, two events directly associated with a successful muscle regenerative response.