| Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages. | |
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MedLine Citation:
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PMID: 20421466 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tim-4 is a phosphatidylserine (PS) receptor that is expressed on various macrophage subsets. It mediates phagocytosis of apoptotic cells by peritoneal macrophages. The in vivo functions of Tim-4 in phagocytosis and immune responses, however, are still unclear. In this study, we show that Tim-4 quickly forms punctate caps on contact with apoptotic cells, in contrast to its normal diffused expression on the surface of phagocytes. Despite its expression in marginal zone and tingible body macrophages, Tim-4 deficiency only minimally affects outcomes of several acute immune challenges, including the trapping of apoptotic cells in the marginal zone, the clearance apoptotic cells by tingible body macrophages, and the formation of germinal centers and elicitation of antibody responses against sheep red blood cells (SRBCs). In addition, Tim-4(-/-) resident peritoneal macrophages (rPMs) phagocytose necrotic cells and other opsonized targets normally. However, their ability to bind and engulf apoptotic cells is significantly compromised both in vitro and in vivo. Most importantly, Tim-4 deficiency results in increased cellularity in the peritoneum. Resting rPMs produce higher TNF-alpha in culture. Their response to LPS, on the contrary, is dampened. Our data support an indispensible role of Tim-4 in maintaining the homeostasis of rPMs. |
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Authors:
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Kit Wong; Patricia A Valdez; Christine Tan; Sherry Yeh; Jo-Anne Hongo; Wenjun Ouyang |
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Publication Detail:
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Type: Journal Article Date: 2010-04-26 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-12 Completed Date: 2010-06-02 Revised Date: 2010-09-30 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 8712-7 Citation Subset: IM |
Affiliation:
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Department of Immunology, Genentech, Inc., South San Francisco, CA 94080, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies / immunology Antibody Formation / immunology Apoptosis / immunology Cell Adhesion Cell Count Cell Line Erythrocytes / immunology Homeostasis / immunology* Humans Hypersensitivity, Delayed / immunology Macrophages, Peritoneal / cytology, immunology* Membrane Proteins / deficiency, metabolism* Mice Phagocytosis / immunology Protein Transport Receptors, Cell Surface / metabolism* Receptors, Complement / immunology Sheep Spleen / cytology, immunology Tumor Necrosis Factor-alpha / biosynthesis |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Membrane Proteins; 0/Receptors, Cell Surface; 0/Receptors, Complement; 0/TIM-4 protein, mouse; 0/Tumor Necrosis Factor-alpha; 0/phosphatidylserine receptor |
| Comments/Corrections | |
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