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Article
Nature Immunology  4, 87 - 91 (2002)
Published online: 25 November 2002; | doi:10.1038/ni871

Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells

Howard A. Anderson1, 6, Caroline A. Maylock2, 6, Joy A. Williams3, Cloud P. Paweletz4, Hongjun Shu5 & Emily Shacter1

1  Laboratory of Biochemistry, Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.

2  Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20815, USA.

3  Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

4  Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

5  Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas, TX 75390, USA.

6  These authors contributed equally to this work.

Correspondence should be addressed to Emily Shacter shacter@cber.fda.gov
Rapid phagocytosis of apoptotic cells is thought to limit the development of inflammation and autoimmune disease. Serum enhances macrophage phagocytosis of apoptotic cells. Here we identified protein S as the factor responsible for serum-stimulated phagocytosis of apoptotic cells. Protein S is best known for its anti-thrombotic activity, serving as a cofactor for protein C. Purified protein S was equivalent to serum in its ability to stimulate macrophage phagocytosis of apoptotic lymphoma cells, and immunodepletion of protein S eliminated the prophagocytic activity of serum. Protein S acted by binding to phosphatidylserine expressed on the apoptotic cell surface. Protein S is thus a multifunctional protein that can facilitate clearance of early apoptotic cells in addition to regulating blood coagulation.

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The role of phosphatidylserine in recognition of apoptotic cells by phagocytes
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RESEARCH
Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death
Cell Death and Differentiation Original Paper (11 Apr 2001)

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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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