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Adiponectin modulates inflammatory reactions via calreticulin receptor–dependent clearance of early apoptotic bodies
Yukihiro Takemura, … , Shinji Kihara, Kenneth Walsh
Yukihiro Takemura, … , Shinji Kihara, Kenneth Walsh
Published February 1, 2007
Citation Information: J Clin Invest. 2007;117(2):375-386. https://doi.org/10.1172/JCI29709.
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Research Article Immunology Article has an altmetric score of 8

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

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Abstract

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.

Authors

Yukihiro Takemura, Noriyuki Ouchi, Rei Shibata, Tamar Aprahamian, Michael T. Kirber, Ross S. Summer, Shinji Kihara, Kenneth Walsh

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Figure 2

Systemic delivery of adiponectin promotes the uptake of apoptotic debris by peritoneal macrophages.

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Systemic delivery of adiponectin promotes the uptake of apoptotic debris...
(A) Strains of mice were injected with Ad–β-gal or Ad-APN on the same day as thioglycollate treatment. Circulating adiponectin levels at the time of sacrifice were 12.5 ± 1.6 μg/ml in B6.lpr/Ad–β-gal and 19.5 ± 2.4 μg/ml in B6.lpr/Ad-APN. TAMRA, SE–labeled apoptotic Jurkat T cells were injected into the peritoneum of the indicated strains of mice 3 days after the administration of thioglycollate. After 30 minutes, peritoneal cells were removed by lavage and subjected to flow cytometry. (B) Phagocytosis was scored as the percentage of F4/80-positive macrophages that also stained positive for TAMRA, SE. Scatter plots show representative flow cytometry data for 3 experimental conditions. Dual-labeled cells are represented in the upper right quadrant. **P < 0.01 versus Ad–β-gal; ††P < 0.01 versus WT (n = 6).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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