Role of granulocyte macrophage colony-stimulating factor during gram-negative lung infection with Pseudomonas aeruginosa.

Ballinger MN, Paine R, Serezani CH, Aronoff DM, Choi ES, Standiford TJ, Toews GB, Moore BB
Am J Respir Cell Mol Biol. 2006 34 (6): 766-74

PMID: 16474098 · PMCID: PMC2644237 · DOI:10.1165/rcmb.2005-0246OC

Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates survival, proliferation, differentiation, and function of myeloid cells. Recently, GM-CSF has been shown to be important for normal pulmonary homeostasis. We report that GM-CSF is induced in lung leukocytes during infection with Gram-negative bacteria. Therefore, we postulated that deficiencies in GM-CSF would increase susceptibility to Gram-negative infection in vivo. After an intratracheal inoculum with Pseudomonas aeruginosa, GM-CSF-/- mice show decreased survival compared with wild-type mice. GM-CSF-/- mice show increased lung, spleen, and blood bacterial CFU. GM-CSF-/- mice are defective in the production of cysteinyl leukotrienes, prostaglandin E2, macrophage inflammatory protein, and keratinocyte-derived chemokine in lung leukocytes postinfection. Despite these defects, inflammatory cell recruitment is not diminished at 6 or 24 h postinfection, and the functional activity of polymorphonuclear leukocytes from the lung and peritoneum against P. aeruginosa is enhanced in GM-CSF-/- mice. In contrast, alveolar macrophage (AM) phagocytosis, killing, and H2O2 production are defective in GM-CSF-/- mice. Although the absence of GM-CSF has profound effects on AMs, peritoneal macrophages seem to have normal bactericidal activities in GM-CSF-/- mice. Defects in AM function may be related to diminished levels of IFN-gamma and TNF-alpha postinfection. Thus, GM-CSF-/- mice are more susceptible to lung infection with P. aeruginosa as a result of impaired AM function.

MeSH Terms (16)

Animals Chemokines, CXC Colony Count, Microbial Cytokines Eicosanoids Granulocyte-Macrophage Colony-Stimulating Factor Leukocytes Lung Macrophages, Alveolar Mice Mice, Inbred C57BL Mice, Knockout Phagocytosis Pneumonia, Bacterial Pseudomonas aeruginosa Pseudomonas Infections

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