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

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.

Loss of Mitochondrial Protein Fus1 Augments Host Resistance to Acinetobacter baumannii Infection

“…Likewise, earlier activation/phosphorylation of the PI3K/Akt/mTOR pathways (Fig. 6a) that is involved in chemotaxis of neutrophils may also be due to higher ROS production in Fus1 Ϫ/Ϫ mice (32)(33)(34). These data introduce the possibility that increased ROS production in Fus1 Ϫ/Ϫ mice contributes to increased NF-B and mTOR pathway activity, which in turn increases neutrophil recruitment (26,27,(35)(36)(37).…”

Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

“…at a dose of 200 ng/ mouse/ day for 7 days starting at 6 d.a.d.s. (within the range of the dose used clinically [39]) (S6H–S6J Fig). Intranasal administration of GM-CSF resulted in less inflammatory cell recruitment (S6D–S6F Fig) and less inflammatory chemokine expression of IP-10 in the BAL at 14 d.a.d.s.…”

Preceding human metapneumovirus infection increases adherence of Streptococcus pneumoniae and severity of murine pneumococcal pneumonia

“…23,24 IL-1a plays an important role in the stimulation of neutrophil chemokines after bacterial infection, 25,26 and granulocyte-macrophage colony-stimulating factor is known as a priming factor and chemoattractant of neutrophils. 27 It appears that IL-1a and TNF-a play overlapping roles in the innate response to S. pneumoniae infection. 28 In mice with preceding influenza infection, impaired expression of neutrophil chemokines (KC and MIP-2) might contribute to decreased recruitment of neutrophils after secondary challenge with S. pneumoniae.…”