Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages
Kupffer cells are endocytic, yet weak producers of proinflammatory cytokines, as compared against splenic and peritoneal macrophages. The immunostimulatory role of Kupffer cells in various inflammatory liver diseases is still not fully understood. In this study, phenotypic and functional aspects of...
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| Veröffentlicht in: | Journal of leukocyte biology 2012-10, Vol.92 (4), p.723-733 |
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| container_title | Journal of leukocyte biology |
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| creator | Movita, Dowty Kreefft, Kim Biesta, Paula Oudenaren, Adri Leenen, Pieter J. M. Janssen, Harry L. A. Boonstra, Andre |
| description | Kupffer cells are endocytic, yet weak producers of proinflammatory cytokines, as compared against splenic and peritoneal macrophages.
The immunostimulatory role of Kupffer cells in various inflammatory liver diseases is still not fully understood. In this study, phenotypic and functional aspects of Kupffer cells from healthy C57BL/6 mice were analyzed and compared with those of splenic and peritoneal macrophages to generate a blueprint of the cells under steady‐state conditions. In the mouse liver, only one population of Kupffer cells was identified as F4/80highCD11blow cells. We observed that freshy isolated Kupffer cells are endocytic and show a relatively high basal ROS content. Interestingly, despite expression of TLR mRNA on Kupffer cells, ligation of TLR4, TLR7/8, and TLR9 resulted in a weak induction of IL‐10, low or undetectable levels of IL‐12p40 and TNF, and up‐regulation of CD40 on the surface. Kupffer cells and splenic macrophages show functional similarities, in comparison with peritoneal macrophages, as reflected by comparable levels of TLR4, TLR7/8, and TLR9 mRNA and low or undetectable levels of TNF and IL‐12p40 produced upon TLR ligation. The unique, functional characteristics of Kupffer cells, demonstrated in this study, suggest that Kupffer cells under steady‐state conditions are specialized as phagocytes to clear and degrade particulates and only play a limited immunoregulatory role via the release of soluble mediators. |
| doi_str_mv | 10.1189/jlb.1111566 |
| format | Article |
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The immunostimulatory role of Kupffer cells in various inflammatory liver diseases is still not fully understood. In this study, phenotypic and functional aspects of Kupffer cells from healthy C57BL/6 mice were analyzed and compared with those of splenic and peritoneal macrophages to generate a blueprint of the cells under steady‐state conditions. In the mouse liver, only one population of Kupffer cells was identified as F4/80highCD11blow cells. We observed that freshy isolated Kupffer cells are endocytic and show a relatively high basal ROS content. Interestingly, despite expression of TLR mRNA on Kupffer cells, ligation of TLR4, TLR7/8, and TLR9 resulted in a weak induction of IL‐10, low or undetectable levels of IL‐12p40 and TNF, and up‐regulation of CD40 on the surface. Kupffer cells and splenic macrophages show functional similarities, in comparison with peritoneal macrophages, as reflected by comparable levels of TLR4, TLR7/8, and TLR9 mRNA and low or undetectable levels of TNF and IL‐12p40 produced upon TLR ligation. The unique, functional characteristics of Kupffer cells, demonstrated in this study, suggest that Kupffer cells under steady‐state conditions are specialized as phagocytes to clear and degrade particulates and only play a limited immunoregulatory role via the release of soluble mediators.</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.1111566</identifier><identifier>PMID: 22685319</identifier><language>eng</language><publisher>United States: Society for Leukocyte Biology</publisher><subject>Animals ; Antigens, CD - analysis ; Antigens, Differentiation, Myelomonocytic - analysis ; CD11b Antigen - analysis ; Cells, Cultured ; endocytosis ; IL‐10 ; immunoregulation ; Interleukin-1 Receptor-Associated Kinases - genetics ; Interleukin-10 - biosynthesis ; Intracellular Signaling Peptides and Proteins - genetics ; Kupffer Cells - physiology ; liver ; Macrophages - physiology ; Macrophages, Peritoneal - physiology ; Mice ; Mice, Inbred C57BL ; Phenotype ; Reactive Oxygen Species - metabolism ; Spleen - immunology ; Toll-Like Receptors - genetics ; Toll-Like Receptors - physiology</subject><ispartof>Journal of leukocyte biology, 2012-10, Vol.92 (4), p.723-733</ispartof><rights>2012 Society for Leukocyte Biology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3603-6183671ac282888ff24fe9873d05726239728cd7cb4120d7e425a7fb067535063</citedby><cites>FETCH-LOGICAL-c3603-6183671ac282888ff24fe9873d05726239728cd7cb4120d7e425a7fb067535063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.1111566$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.1111566$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27907,27908,45557,45558</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22685319$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Movita, Dowty</creatorcontrib><creatorcontrib>Kreefft, Kim</creatorcontrib><creatorcontrib>Biesta, Paula</creatorcontrib><creatorcontrib>Oudenaren, Adri</creatorcontrib><creatorcontrib>Leenen, Pieter J. M.</creatorcontrib><creatorcontrib>Janssen, Harry L. A.</creatorcontrib><creatorcontrib>Boonstra, Andre</creatorcontrib><title>Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><description>Kupffer cells are endocytic, yet weak producers of proinflammatory cytokines, as compared against splenic and peritoneal macrophages.
The immunostimulatory role of Kupffer cells in various inflammatory liver diseases is still not fully understood. In this study, phenotypic and functional aspects of Kupffer cells from healthy C57BL/6 mice were analyzed and compared with those of splenic and peritoneal macrophages to generate a blueprint of the cells under steady‐state conditions. In the mouse liver, only one population of Kupffer cells was identified as F4/80highCD11blow cells. We observed that freshy isolated Kupffer cells are endocytic and show a relatively high basal ROS content. Interestingly, despite expression of TLR mRNA on Kupffer cells, ligation of TLR4, TLR7/8, and TLR9 resulted in a weak induction of IL‐10, low or undetectable levels of IL‐12p40 and TNF, and up‐regulation of CD40 on the surface. Kupffer cells and splenic macrophages show functional similarities, in comparison with peritoneal macrophages, as reflected by comparable levels of TLR4, TLR7/8, and TLR9 mRNA and low or undetectable levels of TNF and IL‐12p40 produced upon TLR ligation. The unique, functional characteristics of Kupffer cells, demonstrated in this study, suggest that Kupffer cells under steady‐state conditions are specialized as phagocytes to clear and degrade particulates and only play a limited immunoregulatory role via the release of soluble mediators.</description><subject>Animals</subject><subject>Antigens, CD - analysis</subject><subject>Antigens, Differentiation, Myelomonocytic - analysis</subject><subject>CD11b Antigen - analysis</subject><subject>Cells, Cultured</subject><subject>endocytosis</subject><subject>IL‐10</subject><subject>immunoregulation</subject><subject>Interleukin-1 Receptor-Associated Kinases - genetics</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Kupffer Cells - physiology</subject><subject>liver</subject><subject>Macrophages - physiology</subject><subject>Macrophages, Peritoneal - physiology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Phenotype</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Spleen - immunology</subject><subject>Toll-Like Receptors - genetics</subject><subject>Toll-Like Receptors - physiology</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEuP1DAQhC0EYoeFE3fkCxISCviR2M6RXfEeiQucLcdpb7xKHGMnCvMP-Nk4moEjp7bUX1W7CqHnlLyhVLVv78euPChthHiADrTlquJC8ofoQGRNq6Ym5Ao9yfmeEMKZII_RFWNCNZy2B_T76xqdg4QtjGPG8CsmyBkbvAb_cwVs56nzwSx-Dnh2OA4Q5uUUvcUm9Nitwe4rM2I7mGTsAsnnxdu8C6NJ0OPNLwPOcYRwEcXCLHOAIpqMTXMczB3kp-iRM2OGZ5d5jX58eP_99lN1_Pbx8-27Y2W5ILwSVJVw1FimmFLKOVY7aJXkPWkkE4y3kinbS9vVlJFeQs0aI11HhGx4QwS_Rq_OvjHNJWBe9OTzHt4EmNesKVGMlRNNU9DXZ7R8MucETsfkJ5NOBdJ79bpUry_VF_rFxXjtJuj_sX-7LgA5A5sf4fQ_L_3leEMk40Xy8iwZ_N2w-QQ6T2YcywWmt21rma71zv0B-dWcxA</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>Movita, Dowty</creator><creator>Kreefft, Kim</creator><creator>Biesta, Paula</creator><creator>Oudenaren, Adri</creator><creator>Leenen, Pieter J. M.</creator><creator>Janssen, Harry L. A.</creator><creator>Boonstra, Andre</creator><general>Society for Leukocyte Biology</general><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>7X8</scope></search><sort><creationdate>20121001</creationdate><title>Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages</title><author>Movita, Dowty ; Kreefft, Kim ; Biesta, Paula ; Oudenaren, Adri ; Leenen, Pieter J. M. ; Janssen, Harry L. A. ; Boonstra, Andre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3603-6183671ac282888ff24fe9873d05726239728cd7cb4120d7e425a7fb067535063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antigens, CD - analysis</topic><topic>Antigens, Differentiation, Myelomonocytic - analysis</topic><topic>CD11b Antigen - analysis</topic><topic>Cells, Cultured</topic><topic>endocytosis</topic><topic>IL‐10</topic><topic>immunoregulation</topic><topic>Interleukin-1 Receptor-Associated Kinases - genetics</topic><topic>Interleukin-10 - biosynthesis</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Kupffer Cells - physiology</topic><topic>liver</topic><topic>Macrophages - physiology</topic><topic>Macrophages, Peritoneal - physiology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Phenotype</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Spleen - immunology</topic><topic>Toll-Like Receptors - genetics</topic><topic>Toll-Like Receptors - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Movita, Dowty</creatorcontrib><creatorcontrib>Kreefft, Kim</creatorcontrib><creatorcontrib>Biesta, Paula</creatorcontrib><creatorcontrib>Oudenaren, Adri</creatorcontrib><creatorcontrib>Leenen, Pieter J. M.</creatorcontrib><creatorcontrib>Janssen, Harry L. A.</creatorcontrib><creatorcontrib>Boonstra, Andre</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of leukocyte biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Movita, Dowty</au><au>Kreefft, Kim</au><au>Biesta, Paula</au><au>Oudenaren, Adri</au><au>Leenen, Pieter J. M.</au><au>Janssen, Harry L. A.</au><au>Boonstra, Andre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages</atitle><jtitle>Journal of leukocyte biology</jtitle><addtitle>J Leukoc Biol</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>92</volume><issue>4</issue><spage>723</spage><epage>733</epage><pages>723-733</pages><issn>0741-5400</issn><eissn>1938-3673</eissn><abstract>Kupffer cells are endocytic, yet weak producers of proinflammatory cytokines, as compared against splenic and peritoneal macrophages.
The immunostimulatory role of Kupffer cells in various inflammatory liver diseases is still not fully understood. In this study, phenotypic and functional aspects of Kupffer cells from healthy C57BL/6 mice were analyzed and compared with those of splenic and peritoneal macrophages to generate a blueprint of the cells under steady‐state conditions. In the mouse liver, only one population of Kupffer cells was identified as F4/80highCD11blow cells. We observed that freshy isolated Kupffer cells are endocytic and show a relatively high basal ROS content. Interestingly, despite expression of TLR mRNA on Kupffer cells, ligation of TLR4, TLR7/8, and TLR9 resulted in a weak induction of IL‐10, low or undetectable levels of IL‐12p40 and TNF, and up‐regulation of CD40 on the surface. Kupffer cells and splenic macrophages show functional similarities, in comparison with peritoneal macrophages, as reflected by comparable levels of TLR4, TLR7/8, and TLR9 mRNA and low or undetectable levels of TNF and IL‐12p40 produced upon TLR ligation. The unique, functional characteristics of Kupffer cells, demonstrated in this study, suggest that Kupffer cells under steady‐state conditions are specialized as phagocytes to clear and degrade particulates and only play a limited immunoregulatory role via the release of soluble mediators.</abstract><cop>United States</cop><pub>Society for Leukocyte Biology</pub><pmid>22685319</pmid><doi>10.1189/jlb.1111566</doi><tpages>11</tpages></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Animals Antigens, CD - analysis Antigens, Differentiation, Myelomonocytic - analysis CD11b Antigen - analysis Cells, Cultured endocytosis IL‐10 immunoregulation Interleukin-1 Receptor-Associated Kinases - genetics Interleukin-10 - biosynthesis Intracellular Signaling Peptides and Proteins - genetics Kupffer Cells - physiology liver Macrophages - physiology Macrophages, Peritoneal - physiology Mice Mice, Inbred C57BL Phenotype Reactive Oxygen Species - metabolism Spleen - immunology Toll-Like Receptors - genetics Toll-Like Receptors - physiology |
| title | Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages |
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