Regulation and function of macrophage colony-stimulating factor (CSF1) in the chicken immune system
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 produce...
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description | 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.
•Two mouse monoclonal antibodies to chicken CSF1 (ROS-AV181 and 183) were produced.•A capture ELISA assays was developed to quantify native circulating CSF1 levels.•Antibody ROS-AV183 was shown to neutralise the bioactivities of CSF1 in vitro.•Treatment of hatchlings using ROS-AV183 in vivo impacted on chicken macrophage subsets and B-cells.•Anti-CSF1 treatment produced a reduction in overall bone density, trabecular volume and TRAP+ osteoclasts. |
doi_str_mv | 10.1016/j.dci.2019.103586 |
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•Two mouse monoclonal antibodies to chicken CSF1 (ROS-AV181 and 183) were produced.•A capture ELISA assays was developed to quantify native circulating CSF1 levels.•Antibody ROS-AV183 was shown to neutralise the bioactivities of CSF1 in vitro.•Treatment of hatchlings using ROS-AV183 in vivo impacted on chicken macrophage subsets and B-cells.•Anti-CSF1 treatment produced a reduction in overall bone density, trabecular volume and TRAP+ osteoclasts.</description><identifier>ISSN: 0145-305X</identifier><identifier>EISSN: 1879-0089</identifier><identifier>DOI: 10.1016/j.dci.2019.103586</identifier><identifier>PMID: 31870792</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Ablation ; Animals ; Antibodies - isolation & purification ; Antibodies, Blocking - isolation & purification ; Avian Proteins - genetics ; Avian Proteins - metabolism ; Biological activity ; Biomedical materials ; Birds ; Bone density ; Bone marrow ; Bursa of Fabricius ; Bursa of Fabricius - metabolism ; Cancellous bone ; Cecum ; Cell Differentiation ; Cell proliferation ; Cells, Cultured ; Chick Embryo ; Chicken ; Chickens ; Chickens - immunology ; Colonies ; Colony-stimulating factor ; CSF1 ; Embryos ; Enzyme-linked immunosorbent assay ; Fc receptors ; Fusion protein ; Gene Expression Regulation, Developmental ; Growth factors ; Hepatocytes ; Immune system ; Immunoglobulin Fc Fragments - genetics ; Immunohistochemistry ; Kupffer cells ; Levels ; Macrophage colony-stimulating factor ; Macrophage Colony-Stimulating Factor - genetics ; Macrophage Colony-Stimulating Factor - immunology ; Macrophage Colony-Stimulating Factor - metabolism ; Macrophages ; Macrophages - physiology ; Monoclonal antibodies ; Monocytes ; Neutralising antibody ; Population studies ; Populations ; Poultry ; Receptor, Macrophage Colony-Stimulating Factor - genetics ; Receptor, Macrophage Colony-Stimulating Factor - metabolism ; Recombinant Fusion Proteins - genetics ; Tissues ; Vertebrates ; Western blotting</subject><ispartof>Developmental and comparative immunology, 2020-04, Vol.105, p.103586-103586, Article 103586</ispartof><rights>2020 The Authors</rights><rights>Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Apr 2020</rights><rights>2020 The Authors 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-eb9c6d67c1e2a6912df5503d978a7e0fe0f5d1172c7bda9afd1f26ae10c3f54b3</citedby><cites>FETCH-LOGICAL-c479t-eb9c6d67c1e2a6912df5503d978a7e0fe0f5d1172c7bda9afd1f26ae10c3f54b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.dci.2019.103586$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31870792$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Zhiguang</creatorcontrib><creatorcontrib>Harne, Rakhi</creatorcontrib><creatorcontrib>Chintoan-Uta, Cosmin</creatorcontrib><creatorcontrib>Hu, Tuan-Jun</creatorcontrib><creatorcontrib>Wallace, Robert</creatorcontrib><creatorcontrib>MacCallum, Amanda</creatorcontrib><creatorcontrib>Stevens, Mark P.</creatorcontrib><creatorcontrib>Kaiser, Pete</creatorcontrib><creatorcontrib>Balic, Adam</creatorcontrib><creatorcontrib>Hume, David A.</creatorcontrib><title>Regulation and function of macrophage colony-stimulating factor (CSF1) in the chicken immune system</title><title>Developmental and comparative immunology</title><addtitle>Dev Comp Immunol</addtitle><description>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.
•Two mouse monoclonal antibodies to chicken CSF1 (ROS-AV181 and 183) were produced.•A capture ELISA assays was developed to quantify native circulating CSF1 levels.•Antibody ROS-AV183 was shown to neutralise the bioactivities of CSF1 in vitro.•Treatment of hatchlings using ROS-AV183 in vivo impacted on chicken macrophage subsets and B-cells.•Anti-CSF1 treatment produced a reduction in overall bone density, trabecular volume and TRAP+ osteoclasts.</description><subject>Ablation</subject><subject>Animals</subject><subject>Antibodies - isolation & purification</subject><subject>Antibodies, Blocking - isolation & purification</subject><subject>Avian Proteins - genetics</subject><subject>Avian Proteins - metabolism</subject><subject>Biological activity</subject><subject>Biomedical materials</subject><subject>Birds</subject><subject>Bone density</subject><subject>Bone marrow</subject><subject>Bursa of Fabricius</subject><subject>Bursa of Fabricius - metabolism</subject><subject>Cancellous bone</subject><subject>Cecum</subject><subject>Cell Differentiation</subject><subject>Cell proliferation</subject><subject>Cells, Cultured</subject><subject>Chick Embryo</subject><subject>Chicken</subject><subject>Chickens</subject><subject>Chickens - immunology</subject><subject>Colonies</subject><subject>Colony-stimulating factor</subject><subject>CSF1</subject><subject>Embryos</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Fc receptors</subject><subject>Fusion protein</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Growth factors</subject><subject>Hepatocytes</subject><subject>Immune system</subject><subject>Immunoglobulin Fc Fragments - genetics</subject><subject>Immunohistochemistry</subject><subject>Kupffer cells</subject><subject>Levels</subject><subject>Macrophage colony-stimulating factor</subject><subject>Macrophage Colony-Stimulating Factor - genetics</subject><subject>Macrophage Colony-Stimulating Factor - immunology</subject><subject>Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Macrophages</subject><subject>Macrophages - physiology</subject><subject>Monoclonal antibodies</subject><subject>Monocytes</subject><subject>Neutralising antibody</subject><subject>Population studies</subject><subject>Populations</subject><subject>Poultry</subject><subject>Receptor, Macrophage Colony-Stimulating Factor - genetics</subject><subject>Receptor, Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Tissues</subject><subject>Vertebrates</subject><subject>Western blotting</subject><issn>0145-305X</issn><issn>1879-0089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1rGzEQhkVpaJy0P6CXIuglPayjD0u7olAopkkLgUA_oDchSyNb7q7kSLsB__sqcRraHDoIhkHPvMzMi9BrSuaUUHm-nTsb5oxQVWsuOvkMzWjXqoaQTj1HM0IXouFE_DxGJ6VsSY2OkhfomFeKtIrNkP0K66k3Y0gRm-iwn6K9L5LHg7E57TZmDdimPsV9U8Yw3NNxjb2xY8r4bPntgr7DIeJxU7lNsL8g4jAMUwRc9mWE4SU68qYv8Oohn6IfF5--Lz83V9eXX5Yfrxq7aNXYwEpZ6WRrKTAjFWXOC0G4U21nWiC-PuEobZltV84o4x31TBqgxHIvFit-ij4cdHfTagBnIY7Z9HqXw2DyXicT9L8_MWz0Ot1qqZSkXFSBsweBnG4mKKMeQrHQ9yZCmopmnBPOhOh4Rd8-QbdpyrGuVynJlBSiZZWiB6oespQM_nEYSvSdhXqrq4X6zkJ9sLD2vPl7i8eOP55V4P0BgHrL2wBZFxsgWnAhgx21S-E_8r8BUfGtzA</recordid><startdate>202004</startdate><enddate>202004</enddate><creator>Wu, Zhiguang</creator><creator>Harne, Rakhi</creator><creator>Chintoan-Uta, Cosmin</creator><creator>Hu, Tuan-Jun</creator><creator>Wallace, Robert</creator><creator>MacCallum, Amanda</creator><creator>Stevens, Mark P.</creator><creator>Kaiser, Pete</creator><creator>Balic, Adam</creator><creator>Hume, David A.</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><general>Elsevier Science</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>202004</creationdate><title>Regulation and function of macrophage colony-stimulating factor (CSF1) in the chicken immune system</title><author>Wu, Zhiguang ; Harne, Rakhi ; Chintoan-Uta, Cosmin ; Hu, Tuan-Jun ; Wallace, Robert ; MacCallum, Amanda ; Stevens, Mark P. ; Kaiser, Pete ; Balic, Adam ; Hume, David A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-eb9c6d67c1e2a6912df5503d978a7e0fe0f5d1172c7bda9afd1f26ae10c3f54b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Ablation</topic><topic>Animals</topic><topic>Antibodies - isolation & purification</topic><topic>Antibodies, Blocking - isolation & purification</topic><topic>Avian Proteins - genetics</topic><topic>Avian Proteins - metabolism</topic><topic>Biological activity</topic><topic>Biomedical materials</topic><topic>Birds</topic><topic>Bone density</topic><topic>Bone marrow</topic><topic>Bursa of Fabricius</topic><topic>Bursa of Fabricius - metabolism</topic><topic>Cancellous bone</topic><topic>Cecum</topic><topic>Cell Differentiation</topic><topic>Cell proliferation</topic><topic>Cells, Cultured</topic><topic>Chick Embryo</topic><topic>Chicken</topic><topic>Chickens</topic><topic>Chickens - immunology</topic><topic>Colonies</topic><topic>Colony-stimulating factor</topic><topic>CSF1</topic><topic>Embryos</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Fc receptors</topic><topic>Fusion protein</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Growth factors</topic><topic>Hepatocytes</topic><topic>Immune system</topic><topic>Immunoglobulin Fc Fragments - genetics</topic><topic>Immunohistochemistry</topic><topic>Kupffer cells</topic><topic>Levels</topic><topic>Macrophage colony-stimulating factor</topic><topic>Macrophage Colony-Stimulating Factor - genetics</topic><topic>Macrophage Colony-Stimulating Factor - immunology</topic><topic>Macrophage Colony-Stimulating Factor - metabolism</topic><topic>Macrophages</topic><topic>Macrophages - physiology</topic><topic>Monoclonal antibodies</topic><topic>Monocytes</topic><topic>Neutralising antibody</topic><topic>Population studies</topic><topic>Populations</topic><topic>Poultry</topic><topic>Receptor, Macrophage Colony-Stimulating Factor - genetics</topic><topic>Receptor, Macrophage Colony-Stimulating Factor - metabolism</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Tissues</topic><topic>Vertebrates</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Zhiguang</creatorcontrib><creatorcontrib>Harne, Rakhi</creatorcontrib><creatorcontrib>Chintoan-Uta, Cosmin</creatorcontrib><creatorcontrib>Hu, Tuan-Jun</creatorcontrib><creatorcontrib>Wallace, Robert</creatorcontrib><creatorcontrib>MacCallum, Amanda</creatorcontrib><creatorcontrib>Stevens, Mark P.</creatorcontrib><creatorcontrib>Kaiser, Pete</creatorcontrib><creatorcontrib>Balic, Adam</creatorcontrib><creatorcontrib>Hume, David A.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Developmental and comparative immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Zhiguang</au><au>Harne, Rakhi</au><au>Chintoan-Uta, Cosmin</au><au>Hu, Tuan-Jun</au><au>Wallace, Robert</au><au>MacCallum, Amanda</au><au>Stevens, Mark P.</au><au>Kaiser, Pete</au><au>Balic, Adam</au><au>Hume, David A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation and function of macrophage colony-stimulating factor (CSF1) in the chicken immune system</atitle><jtitle>Developmental and comparative immunology</jtitle><addtitle>Dev Comp Immunol</addtitle><date>2020-04</date><risdate>2020</risdate><volume>105</volume><spage>103586</spage><epage>103586</epage><pages>103586-103586</pages><artnum>103586</artnum><issn>0145-305X</issn><eissn>1879-0089</eissn><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.
•Two mouse monoclonal antibodies to chicken CSF1 (ROS-AV181 and 183) were produced.•A capture ELISA assays was developed to quantify native circulating CSF1 levels.•Antibody ROS-AV183 was shown to neutralise the bioactivities of CSF1 in vitro.•Treatment of hatchlings using ROS-AV183 in vivo impacted on chicken macrophage subsets and B-cells.•Anti-CSF1 treatment produced a reduction in overall bone density, trabecular volume and TRAP+ osteoclasts.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>31870792</pmid><doi>10.1016/j.dci.2019.103586</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Ablation Animals Antibodies - isolation & purification Antibodies, Blocking - isolation & purification Avian Proteins - genetics Avian Proteins - metabolism Biological activity Biomedical materials Birds Bone density Bone marrow Bursa of Fabricius Bursa of Fabricius - metabolism Cancellous bone Cecum Cell Differentiation Cell proliferation Cells, Cultured Chick Embryo Chicken Chickens Chickens - immunology Colonies Colony-stimulating factor CSF1 Embryos Enzyme-linked immunosorbent assay Fc receptors Fusion protein Gene Expression Regulation, Developmental Growth factors Hepatocytes Immune system Immunoglobulin Fc Fragments - genetics Immunohistochemistry Kupffer cells Levels Macrophage colony-stimulating factor Macrophage Colony-Stimulating Factor - genetics Macrophage Colony-Stimulating Factor - immunology Macrophage Colony-Stimulating Factor - metabolism Macrophages Macrophages - physiology Monoclonal antibodies Monocytes Neutralising antibody Population studies Populations Poultry Receptor, Macrophage Colony-Stimulating Factor - genetics Receptor, Macrophage Colony-Stimulating Factor - metabolism Recombinant Fusion Proteins - genetics Tissues Vertebrates Western blotting |
title | Regulation and function of macrophage colony-stimulating factor (CSF1) in the chicken immune system |
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