Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Augments Acute Lung Injury via Its Neutrophil Priming Effects.
10.3346/jkms.2008.23.2.288
- Author:
Jae Chol CHOI
1
;
Jae Woo JUNG
;
Hee Won KWAK
;
Ju Han SONG
;
Eun Ju JEON
;
Jong Wook SHIN
;
In Won PARK
;
Byoung Whui CHOI
;
Jae Yeol KIM
Author Information
1. Department of Internal Medicine, Chung Ang University College of Medicine, Seoul, Korea. jykimmd@cau.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Granulocyte-Macrophage Colony-Stimulating Factor;
Adult, Respiratory Distress Syndrome;
Lipopolysaccharides;
Hemorrhage;
Neutrophils
- MeSH:
Animals;
Bone Marrow Cells/cytology;
Chemokine CXCL2/metabolism;
Granulocyte-Macrophage Colony-Stimulating Factor/metabolism/*physiology;
Interleukin-1beta/metabolism;
Lipopolysaccharides/metabolism;
Lung/metabolism/pathology;
*Lung Injury;
Male;
Mice;
Mice, Inbred BALB C;
Mice, Inbred C57BL;
Mice, Transgenic;
Neutrophils/*cytology/metabolism;
Peroxidase/metabolism;
Tumor Necrosis Factor-alpha/metabolism
- From:Journal of Korean Medical Science
2008;23(2):288-295
- CountryRepublic of Korea
- Language:English
-
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-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 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-1beta, 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.
