Abstract
Macrophage colony-stimulating factor (CSF1) is an essential growth factor to control the proliferation, differentiation and survival of cells of the macrophage lineage in vertebrates. We have previously produced a recombinant chicken CSF1-Fc fusion protein and administrated it to birds which produced a substantial expansion of tissue macrophage populations. To further study the biology of CSF1 in the chicken, here we generated anti-chicken CSF1 antibodies (ROS-AV181 and 183) using CSF1-Fc as an immunogen. The specific binding of each monoclonal antibody was confirmed by ELISA, Western blotting and immunohistochemistry on tissue sections. Using the anti-CSF1 antibodies, we show that chicken bone marrow derived macrophages (BMDM) express CSF1 on their surface, and that the level appears to be regulated further by exogenous CSF1. By capture ELISA circulating CSF1 levels increased transiently in both layer and broiler embryos around the day of hatch. The levels of CSF1 in broilers was higher than in layers during the first week after hatch. Antibody ROS-AV183 was able to block CSF1 biological activity in vitro and treatment of hatchlings using this neutralising antibody in vivo impacted on some tissue macrophage populations, but not blood monocytes. After anti-CSF1 treatment, CSF1R-transgene reporter expressing cells were reduced in the bursa of Fabricius and cecal tonsil and TIM4+ Kupffer cells in the liver were almost completely ablated. Anti-CSF1 treatment also produced a reduction in overall bone density, trabecular volume and TRAP+ osteoclasts. Our novel neutralising antibody provides a new tool to study the roles of CSF1 in birds.
Highlights
Macrophage colony-stimulating factor (CSF1) controls the proliferation, differentiation and survival of cells of the macrophage lineage in mammals and birds (Chitu and Stanley, 2017; Garceau et al, 2015; Hume et al, 2019; Jenkins and Hume, 2014; Jenkins et al, 2013)
Production of two monoclonal antibodies to chicken CSF1 and prediction of CSF1 isoforms
To generate anti-CSF1 monoclonal antibodies, mice were immunized with chicken CSF1-Fc
Summary
Macrophage colony-stimulating factor (CSF1) controls the proliferation, differentiation and survival of cells of the macrophage lineage in mammals and birds (Chitu and Stanley, 2017; Garceau et al, 2015; Hume et al, 2019; Jenkins and Hume, 2014; Jenkins et al, 2013). A second ligand for CSF1R, interleukin 34 (IL-34) has been identified (Lin et al., 2008); its expression is more tissue restricted than CSF1 (Wang et al, 2012) and the functions and signalling activities of these CSF1R ligands are not identical (Chihara et al, 2010; Liu et al, 2012; Wei et al, 2010). Both chicken CSF-1 and IL-34 were shown to elicit macrophage growth from chicken BM cells in culture (Garceau et al, 2010). Mutation of Csf in mice (op/op) produces a substantial reduction of tissue macrophage populations alongside pleiotropic impacts on somatic growth and development and variable impacts in cancer and inflammatory disease models (Chitu and Stanley, 2006)
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