Role of granulocyte macrophage colony-stimulating factor during gram-negative lung infection with Pseudomonas aeruginosa.
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.
Immunology Graduate Program, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109-0642, USA.
Megan N
MN
Ballinger
Robert
R
Paine
Carlos H C
CH
Serezani
David M
DM
Aronoff
Esther S
ES
Choi
Theodore J
TJ
Standiford
Galen B
GB
Toews
Bethany B
BB
Moore
D000818:Animals; D019743:Chemokines, CXC / Q000378:metabolism; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*
D019743:Chemokines, CXC; D016207:Cytokines; D015777:Eicosanoids; D016178:Granulocyte-Macrophage Colony-Stimulating Factor