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Artigo Produção Nacional Revisado por pares
BIBTEX RIS

Granulocyte-macrophage colony-stimulating factor (GM-CSF): a chemoattractive agent for murine leukocytes in vivo

2011; Oxford University Press; Volume: 89; Issue: 6 Linguagem: Inglês

10.1189/jlb.0809546

ISSN

1938-3673

Autores

Maitham A. Khajah, Brandie Millen, Denise Carmona Cara, Christopher C. M. Waterhouse, Donna‐Marie McCafferty,

Tópico(s)

Blood disorders and treatments

Resumo

ABSTRACT GM-CSF is well recognized as a proliferative agent for hematopoietic cells and exerts a priming function on neutrophils. The aim of this study was to determine if GM-CSF has a role as a neutrophil chemoattractant in vivo and if it can contribute to recruitment during intestinal inflammation. Initial studies in vitro, using the under-agarose gel assay, determined that GM-CSF can induce neutrophil migration at a much lower molar concentration than the fMLP-like peptide WKYMVm (33.5–134 nM vs. 1–10 μM). GM-CSF-induced neutrophil migration was ablated (<95%) using neutrophils derived from GMCSFRβ−/− mice and significantly attenuated by 42% in PI3Kγ−/−neutrophils. In vivo, a significant increase in leukocyte recruitment was observed using intravital microscopy 4 h post-GM-CSF (10 μg/kg) injection, which was comparable with leukocyte recruitment induced by KC (40 μg/kg). GM-CSF-induced recruitment was abolished, and KC-induced recruitment was maintained in GMCSFRβ−/− mice. Furthermore, in vivo migration of extravascular leukocytes was observed toward a gel containing GM-CSF in WT but not GMCSFRβ−/− mice. Finally, in a model of intestinal inflammation (TNBS-induced colitis), colonic neutrophil recruitment, assessed using the MPO assay, was attenuated significantly in anti-GM-CSF-treated mice or GMCSFRβ−/− mice. These data demonstrate that GM-CSF is a potent chemoattractant in vitro and can recruit neutrophils from the microvasculature and induce extravascular migration in vivo in a β subunit-dependent manner. This property of GM-CSF may contribute significantly to recruitment during intestinal inflammation.

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