title: Control of CSF-1 induced inflammation in teleost fish by a soluble form of the CSF-1 receptor.
abstract: The colony-stimulating factor-1 (CSF-1) is the principal regulator of the survival, proliferation, differentiation, and function of macrophages and their precursors, and has been shown to play a role in the etiology of inflammation. We recently identified a novel mechanism for the control of CSF-1 activity in teleost fish, through the production of an inhibitory soluble form of the CSF-1 receptor (sCSF-1R). Primary goldfish kidney macrophages selectively expressed sCSF-1R during the senescence phase, which corresponds to a defined stage of in vitro culture development where inhibition of macrophage proliferation and apoptotic cell death are prominent. In contrast, primary macrophage cultures undergoing active proliferation displayed low levels of sCSF-1R expression. Addition of purified recombinant sCSF-1R to developing primary macrophage cultures leads to a dose-dependent decrease in macrophage proliferation and inhibits macrophage antimicrobial functions including chemotaxis, phagocytosis, and production of reactive oxygen intermediates. Using a goldfish in vivo model of self-resolving peritonitis, we found that sCSF-1R plays a role in the inhibition of inflammation, following an initial acute phase of antimicrobial responses within an inflammatory site. Soluble CSF-1R inhibits pro-inflammatory cytokine production, inhibits leukocyte recruitment to the inflammatory site and decreases ROS production in a dose-dependent manner. This sCSF-1R-dependent regulation of inflammation appears to be an elegant mechanism for the control of macrophage numbers at inflammatory sites of lower vertebrates. Overall, our results provide new insights into the evolutionary origins of the CSF-1 immune regulatory axis.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Aja M
authors.initials: AM
authors.lastname: Rieger
authors.affiliation: School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Hanington
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada; School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Belosevic
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada; Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. Electronic address: dan.barreda@ualberta.ca.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Barreda
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006054:Goldfish / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000276:immunology*
chemical_list: D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: CSF-1; Evolution; Inflammation; Macrophage; Teleost fish