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Ann Marie LeVine, Jacquelyn A. Reed, Kim E. Kurak, Eli Cianciolo, Jeffrey A. Whitsett
J Clin Invest. 1999;
103(4):563
doi:10.1172/JCI5212
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ranulocyte-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.
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