Granulocyte macrophage-colony stimulating factor (GM-CSF) augments acute lung injury via its neutrophil priming effects
- Authors
- Choi, Jae Chol; Jung, Jae Woo; Kwak, Hee Won; Song, Ju Han; Jeon, Eun Ju; Shin, Jong Wook; Park, In Won; Choi, Byoung Whui; Kim, Jae Yeol
- Issue Date
- Apr-2008
- Publisher
- KOREAN ACAD MEDICAL SCIENCES
- Keywords
- granulocyte-macrophage colony-stimulating factor; adult; respiratory distress syndrome; lipopolysaccharides; hemorrhage; neutrophils
- Citation
- JOURNAL OF KOREAN MEDICAL SCIENCE, v.23, no.2, pp 288 - 295
- Pages
- 8
- Journal Title
- JOURNAL OF KOREAN MEDICAL SCIENCE
- Volume
- 23
- Number
- 2
- Start Page
- 288
- End Page
- 295
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/23792
- DOI
- 10.3346/jkms.2008.23.2.288
- ISSN
- 1011-8934
1598-6357
- Abstract
- 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-a (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin-1 beta (IL-1 beta), 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-1 beta 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 electropnoretic 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-1 beta, which was mediated by increased intra-nuclear translocation of NF-kappa B. 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.
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