Targeting Rac1 signaling inhibits streptococcal M1 protein-induced CXC chemokine formation, neutrophil infiltration and lung injury.
MouseOtherC57BL/6Malen = n = 5 or more per group for most endpoints; n = 3 for Rac1…Intraperitoneal0.5 or 5 mg/kg10 min before M1 protein challenge
Model: Streptococcal M1 protein-induced acute lung injury, 15 ug M1 protein in phosphate-buffered saline intravenously
NSC23766 at 5 mg/kg reduced lung oedema by 87% (wet to dry ratio 5.2 +/- 0.06 to 4.7 +/- 0.03), lung myeloperoxidase by 48% and lavage neutrophils by 65%, and cut CXCL1 and CXCL2 formation by more than 85% without affecting neutrophil Mac-1 up-regulation.
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