Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-targeted mice (GM–/–) cleared group B streptococcus (GBS) from the lungs more slowly than wild-type mice. Expression of GM-CSF in the respiratory epithelium of GM–/– mice improved bacterial clearance to levels greater than that in wild-type GM+/+ mice. Acute aerosolization of GM-CSF to GM+/+ mice significantly enhanced clearance of GBS at 24 hours. GBS infection was associated with increased neutrophilic infiltration in lungs of GM–/– mice, while macrophage infiltrates predominated in wild-type mice, suggesting an abnormality in macrophage clearance of bacteria in the absence of GM-CSF. While phagocytosis of GBS was unaltered, production of superoxide radicals and hydrogen peroxide was markedly deficient in macrophages from GM–/– mice. Lipid peroxidation, assessed by measuring the isoprostane 8-iso-PGF2α, was decreased in the lungs of GM–/– mice. GM-CSF plays an important role in GBS clearance in vivo, mediated in part by its role in enhancing superoxide and hydrogen peroxide production and bacterial killing by alveolar macrophages.
Ann Marie LeVine, Jacquelyn A. Reed, Kim E. Kurak, Eli Cianciolo, Jeffrey A. Whitsett