Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells.
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.
Anderson
Howard A
HA
Laboratory of Biochemistry, Division of Therapeutic Proteins, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Maylock
Caroline A
CA
Williams
Joy A
JA
Paweletz
Cloud P
CP
Shu
Hongjun
H
Shacter
Emily
E
D017209:Apoptosis / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D010718:Phosphatidylserines / Q000097:blood*; D011485:Protein Binding; D017293:Protein S / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D010718:Phosphatidylserines; D017293:Protein S