Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies

Obesity and type 2 diabetes are associated with chronic inflammation. Adiponectin is an adipocyte-derived hormone with antidiabetic and antiinflammatory actions. Here, we demonstrate what we believe to be a previously undocumented activity of adiponectin, facilitating the uptake of early apoptotic c...

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Bibliographic Details
Published in:The Journal of clinical investigation 2007-02, Vol.117 (2), p.375-386
Main Authors: Takemura, Yukihiro, Ouchi, Noriyuki, Shibata, Rei, Aprahamian, Tamar, Kirber, Michael T, Summer, Ross S, Kihara, Shinji, Walsh, Kenneth
Format: Article
Language:English
Subjects:
Adiponectin - deficiency
Adiponectin - genetics
Adiponectin - pharmacology
Adiponectin - physiology
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Base Sequence
Biomedical research
Body fat
Calreticulin - physiology
Cell death
Cell Line
Cytokines
Diabetes
DNA Primers - genetics
Humans
Immune system
Inflammation
Inflammation - etiology
Inflammation - pathology
Inflammation - physiopathology
Inflammation - prevention & control
Jurkat Cells
Mice
Mice, Inbred C57BL
Mice, Inbred MRL lpr
Mice, Knockout
Obesity
Plasma
Proteins
Recombinant Proteins - pharmacology
Surfactants
Type 2 diabetes
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Summary:Obesity and type 2 diabetes are associated with chronic inflammation. Adiponectin is an adipocyte-derived hormone with antidiabetic and antiinflammatory actions. Here, we demonstrate what we believe to be a previously undocumented activity of adiponectin, facilitating the uptake of early apoptotic cells by macrophages, an essential feature of immune system function. Adiponectin-deficient (APN-KO) mice were impaired in their ability to clear apoptotic thymocytes in response to dexamethasone treatment, and these animals displayed a reduced ability to clear early apoptotic cells that were injected into their intraperitoneal cavities. Conversely, adiponectin administration promoted the clearance of apoptotic cells by macrophages in both APN-KO and wild-type mice. Adiponectin overexpression also promoted apoptotic cell clearance and reduced features of autoimmunity in lpr mice whereas adiponectin deficiency in lpr mice led to a further reduction in apoptotic cell clearance, which was accompanied by exacerbated systemic inflammation. Adiponectin was capable of opsonizing apoptotic cells, and phagocytosis of cell corpses was mediated by the binding of adiponectin to calreticulin on the macrophage cell surface. We propose that adiponectin protects the organism from systemic inflammation by promoting the clearance of early apoptotic cells by macrophages through a receptor-dependent pathway involving calreticulin.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci29709