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

被引:329
作者
Anderson, HA
Maylock, CA
Williams, JA
Paweletz, CP
Shu, HJ
Shacter, E [1 ]
机构
[1] US FDA, Biochem Lab, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA
[2] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20815 USA
[3] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA
[4] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA
[5] Univ Texas, Dept Pharmacol, SW Med Ctr, Dallas, TX 75390 USA
关键词
D O I
10.1038/ni871
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:87 / 91
页数:5
相关论文
共 42 条
  • [11] INFLAMMATION - THEYRE NOT JUST FOR CLOTS ANYMORE
    ESMON, CT
    [J]. CURRENT BIOLOGY, 1995, 5 (07) : 743 - 746
  • [12] A receptor for phosphatidylserine-specific clearance of apoptotic cells
    Fadok, VA
    Bratton, DL
    Rose, DM
    Pearson, A
    Ezekewitz, RAB
    Henson, PM
    [J]. NATURE, 2000, 405 (6782) : 85 - 90
  • [13] FADOK VA, 1992, J IMMUNOL, V148, P2207
  • [14] Macrophage and retinal pigment epithelium phagocytosis:: Apoptotic cells and photoreceptors compete for αvβ3 and αvβ5 integrins, and protein kinase C regulates αvβ5 binding and cytoskeletal linkage
    Finnemann, SC
    Rodriguez-Boulan, E
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (06) : 861 - 874
  • [15] Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa
    Gal, A
    Li, Y
    Thompson, DA
    Weir, J
    Orth, U
    Jacobson, SG
    Apfelstedt-Sylla, E
    Vollrath, D
    [J]. NATURE GENETICS, 2000, 26 (03) : 270 - 271
  • [16] REEVALUATION OF THE ROLES OF PROTEIN-S AND GAS6 AS LIGANDS FOR THE RECEPTOR TYROSINE KINASE RSE/TYRO-3
    GODOWSKI, PJ
    MARK, MR
    CHEN, JA
    SADICK, MD
    RAAB, H
    HAMMOND, RG
    [J]. CELL, 1995, 82 (03) : 355 - 358
  • [17] Outer segment phagocytosis by cultured retinal pigment epithelial cells requires Gas6
    Hall, MO
    Prieto, AL
    Obin, MS
    Abrams, TA
    Burgess, BL
    Heeb, MJ
    Agnew, BJ
    [J]. EXPERIMENTAL EYE RESEARCH, 2001, 73 (04) : 509 - 520
  • [18] Identification of a factor that links apoptotic cells to phagocytes
    Hanayama, R
    Tanaka, M
    Miwa, K
    Shinohara, A
    Iwamatsu, A
    Nagata, S
    [J]. NATURE, 2002, 417 (6885) : 182 - 187
  • [19] Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6
    Ishimoto, Y
    Ohashi, K
    Mizuno, K
    Nakano, T
    [J]. JOURNAL OF BIOCHEMISTRY, 2000, 127 (03) : 411 - 417
  • [20] Exposure of phosphatidylserine is a general feature in the phagocytosis of apoptotic lymphocytes by macrophages
    Krahling, S
    Callahan, MK
    Williamson, P
    Schlegel, RA
    [J]. CELL DEATH AND DIFFERENTIATION, 1999, 6 (02) : 183 - 189