| First Author | Khajah M | Year | 2011 |
| Journal | J Leukoc Biol | Volume | 89 |
| Issue | 6 | Pages | 945-53 |
| PubMed ID | 21393420 | Mgi Jnum | J:174736 |
| Mgi Id | MGI:5140679 | Doi | 10.1189/jlb.0809546 |
| Citation | Khajah M, et al. (2011) Granulocyte-macrophage colony-stimulating factor (GM-CSF): a chemoattractive agent for murine leukocytes in vivo. J Leukoc Biol 89(6):945-53 |
| abstractText | 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 muM). GM-CSF-induced neutrophil migration was ablated (<95%) using neutrophils derived from GMCSFRbeta(-/-) mice and significantly attenuated by 42% in PI3Kgamma(-/-)neutrophils. In vivo, a significant increase in leukocyte recruitment was observed using intravital microscopy 4 h post-GM-CSF (10 mug/kg) injection, which was comparable with leukocyte recruitment induced by KC (40 mug/kg). GM-CSF-induced recruitment was abolished, and KC-induced recruitment was maintained in GMCSFRbeta(-/-) mice. Furthermore, in vivo migration of extravascular leukocytes was observed toward a gel containing GM-CSF in WT but not GMCSFRbeta(-/-) 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 GMCSFRbeta(-/-) 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 beta subunit-dependent manner. This property of GM-CSF may contribute significantly to recruitment during intestinal inflammation. |
