Granulocyte colony-stimulating factor and neutrophils--forgotten mediators of inflammatory disease.
Recent studies have highlighted the functional capacity of neutrophils as powerful mediators of tissue inflammation. Granule-packaged proteases and reactive oxygen intermediates, which are important for intracellular digestion during phagocytosis, are released from neutrophils during inflammation. In the extracellular environment, neutrophil-derived proteases can cause local tissue damage, but also regulate the activity of cytokines, cytokine receptors and chemokines. Neutrophils can themselves produce an array of inflammatory mediators, including cytokines, chemokines and complement; these cells also express Fc receptors, which can bind and possibly transport immune complexes into the extravascular compartment, as well as activating neutrophils at opsonised surfaces. Blood-borne neutrophils interact with, and then exit through, the endothelium of blood vessels, after which these cells die and must be removed safely. The balance between neutrophil survival and clearance is crucial to the resolution of inflammation. A major regulator of neutrophil production and survival is the cytokine granulocyte colony-stimulating factor (G-CSF). Treatment with G-CSF can exacerbate underlying inflammatory diseases in humans and mice, and G-CSF deficiency is profoundly protective against collagen-induced arthritis in mice. These findings implicate G-CSF as an important proinflammatory cytokine. This article discusses the roles of neutrophils and G-CSF during chronic inflammatory diseases.
Eyles
Jo L
JL
Reid Rheumatology Laboratory, Division of Autoimmunity and Transplantation, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Roberts
Andrew W
AW
Metcalf
Donald
D
Wicks
Ian P
IP
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism
D016179:Granulocyte Colony-Stimulating Factor