Granulocyte macrophage-colony stimulating factor (GM-CSF) augments acute lung injury via its neutrophil priming effects.
Granulocyte macrophage-colony stimulating factor (GM-CSF) has immuno-stimulatory effects. We hypothesized that GM-CSF plays an important role both in lipopolysaccharide (LPS)- and hemorrhage-induced acute lung injury (ALI). We also postulated that GM-CSF augments LPS-induced inflammation by priming neutrophils. ALI was induced in GM-CSF-/- or control C57BL mice either by LPS injection or by hemorrhage. Lung inflammation (by lung expression for tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin-1beta (IL-1beta), interleukin- 6 (IL-6), and keratinocyte-derived chemokine) and lung injury (by myeloperoxidase and Evans blue dye assay) were evaluated after ALI. Incremental doses of LPS (0, 1, 10, and 100 ng/mL) and GM-CSF (0, 1, 10, and 100 ng/mL) were added to bone marrow neutrophils. The expression of TNF-alpha, MIP-2, and IL-1beta was evaluated with enzyme linked immunosorbent assay. The mRNA expression of three cytokines, and the nuclear translocation of nuclear factor kappa B (NF kappa-B) were evaluated by reverse transcriptase-polymerase chain reaction and electrophoretic mobility shift assay, respectively. GM-CSF -/- mice showed decreased neutrophil infiltration, less leakage, and lower expression of cytokines in the lung after LPS or hemorrhage. GM-CSF augmented LPS-induced protein and mRNA expression of TNF-alpha, MIP-2 and IL-1beta, which was mediated by increased intra-nuclear translocation of NF-kappaB. GM-CSF plays an important role in high-dose LPS and hemorrhage-induced ALI, which appears to be mediated by its priming effect on neutrophils.
Choi
Jae Chol
JC
Department of Internal Medicine, Chung Ang University College of Medicine, 224-1 Heukseok-dong, Dongjak-gu, Seoul, Korea.
Jung
Jae Woo
JW
Kwak
Hee Won
HW
Song
Ju Han
JH
Jeon
Eun Ju
EJ
Shin
Jong Wook
JW
Park
In Won
IW
Choi
Byoung Whui
BW
Kim
Jae Yeol
JY
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D054426:Chemokine CXCL2 / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009195:Peroxidase