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

Am J Respir Cell Mol Biol. 2006 Jun;34(6):766-74. doi: 10.1165/rcmb.2005-0246OC. Epub 2006 Feb 10.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Chemokines, CXC / metabolism
  • Colony Count, Microbial
  • Cytokines / metabolism
  • Eicosanoids / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Leukocytes / microbiology
  • Lung / immunology
  • Lung / metabolism*
  • Lung / microbiology
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phagocytosis
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / metabolism*
  • Pneumonia, Bacterial / microbiology
  • Pseudomonas Infections / immunology
  • Pseudomonas Infections / metabolism*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / isolation & purification*


  • Chemokines, CXC
  • Cytokines
  • Eicosanoids
  • Granulocyte-Macrophage Colony-Stimulating Factor