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Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in
H Takahama1, R Itoh, C Inoue-Komatsu
1Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
Abstract:
Increases in the number and activity of peripheral polymorphonuclear neutrophils (PMNs) is often found in Behçet's disease (BD), indicating that PMN may play an important role in the pathogenesis of this disorder. It has recently been reported that G-CSF and GM-CSF, a family of hematopoietic growth factors, enhance PMN activity. To explore the role of these two CSFs in BD, we first examined the chemotactic response of PMNs to these CSFs by performing a polarization assay. PMN response to G-CSF in BD patients was lower than that in controls, while PMN response to GM-CSF was similar in patients and controls. However, PMNs from BD patients showed an enhanced chemotactic response to N-formyl-L-methionyl-leucyl-phenylalanine. Thus, it is speculated that the PMNs of the patients might have already been activated in vivo by G-CSF and thus could not respond further to this agent in vitro. We examined G-CSF and GM-CSF mRNA expressions in peripheral mononuclear cells stimulated with LPS, PMA, and Con A by Northern hybridization. G-CSF mRNA expression levels in BD patients were higher than in the controls, while GM-CSF mRNA expression levels were lower than in the controls. We also examined the serum levels of the two CSFs by ELISA and EIA. However, all levels of the two CSFs in both patients and controls were not detectable, except in the case of one BD patient in the active stage of the disease, who showed high levels of G-CSF, but not of GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Polymorphonuclear neutrophils (PMNs) in Behçet's disease (BD) show altered responses to granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), suggesting in vivo activation. G-CSF mRNA levels are elevated in BD patients.
Area of Science:
- Immunology
- Hematology
- Rheumatology
Background:
- Behçet's disease (BD) is associated with increased peripheral polymorphonuclear neutrophils (PMNs).
- Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are hematopoietic growth factors that enhance PMN activity.
Purpose of the Study:
- To investigate the role of G-CSF and GM-CSF in the pathogenesis of Behçet's disease.
- To examine the chemotactic response of PMNs to G-CSF and GM-CSF in BD patients.
Main Methods:
- Chemotaxis assays were performed to evaluate PMN polarization in response to G-CSF and GM-CSF.
- Northern hybridization was used to analyze G-CSF and GM-CSF mRNA expression in peripheral mononuclear cells.
- Enzyme-linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA) were employed to measure serum levels of G-CSF and GM-CSF.
Main Results:
- PMN response to G-CSF was reduced in BD patients compared to controls, while response to GM-CSF was similar.
- PMNs from BD patients exhibited an enhanced chemotactic response to N-formyl-L-methionyl-leucyl-phenylalanine.
- G-CSF mRNA expression was higher in BD patients, whereas GM-CSF mRNA expression was lower.
- Serum G-CSF levels were elevated in one active BD patient, but GM-CSF levels were not significantly different.
Conclusions:
- PMNs in BD patients may be pre-activated in vivo, potentially by G-CSF, leading to diminished in vitro responsiveness.
- Altered G-CSF and GM-CSF expression and PMN activity may contribute to the pathogenesis of Behçet's disease.