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PMID:14634079

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Citation

Tada, K, Tanaka, M, Hanayama, R, Miwa, K, Shinohara, A, Iwamatsu, A and Nagata, S (2003) Tethering of apoptotic cells to phagocytes through binding of CD47 to Src homology 2 domain-bearing protein tyrosine phosphatase substrate-1. J. Immunol. 171:5718-26

Abstract

Apoptotic cells are swiftly phagocytosed by macrophages and immature dendritic cells. In this study, we found that one mouse macrophage cell line (BAM3) engulfed apoptotic thymocytes, but not a lymphoma cell line (WR19L). mAbs that inhibited the phagocytosis of apoptotic thymocytes by BAM3 were identified. Purification of the Ag revealed that it was Src homology 2 domain-bearing protein tyrosine phosphatase substrate-1 (SHPS-1). CD47, the ligand for SHPS-1, was expressed in mouse thymocytes, but not in WR19L. When WR19L was transformed with CD47, the transformants, after induction of apoptosis, could be phagocytosed by BAM3. The WR19L transformants expressing CD47 were more efficiently engulfed in vivo by splenic dendritic cells than the parental WR19L. Masking of the phosphatidylserine exposed on apoptotic thymocytes inhibited the engulfment, whereas the anti-SHPS-1 mAb inhibited not only the engulfment, but also the binding of apoptotic cells to phagocytes. These results indicate that macrophages require CD47 and phosphatidylserine on apoptotic cells for engulfment, and suggest that the interaction between CD47 and SHPS-1 works as a tethering step in the phagocytosis.

Links

PubMed

Keywords

Animals; Antibodies, Monoclonal/metabolism; Antigens, CD/metabolism; Antigens, CD/physiology; Antigens, CD47; Antigens, Differentiation; Apoptosis/immunology; Carrier Proteins/metabolism; Carrier Proteins/physiology; Cell Line; Cell Line, Tumor; Cricetinae; Cricetulus; Female; Humans; Macrophages/immunology; Macrophages/metabolism; Membrane Glycoproteins/immunology; Membrane Glycoproteins/isolation & purification; Membrane Glycoproteins/metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; NIH 3T3 Cells; Neural Cell Adhesion Molecule L1/immunology; Neural Cell Adhesion Molecule L1/isolation & purification; Neural Cell Adhesion Molecule L1/metabolism; Phagocytes/enzymology; Phagocytes/immunology; Phagocytes/metabolism; Phagocytosis/immunology; Phosphatidylserines/physiology; Protein Binding/immunology; Protein Tyrosine Phosphatases/metabolism; Receptors, Immunologic; Substrate Specificity/immunology; src Homology Domains/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SHPS1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q61735

F

Seeded From UniProt

complete

MOUSE:SHPS1

located_in

GO:0005887: integral component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SHPS1

acts_upstream_of_or_within

GO:0006911: phagocytosis, engulfment

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SHPS1

acts_upstream_of_or_within

GO:0006910: phagocytosis, recognition

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SHPS1

acts_upstream_of_or_within

GO:0050766: positive regulation of phagocytosis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CD47

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P97797

F

Seeded From UniProt

complete

MOUSE:CD47

located_in

GO:0005887: integral component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CD47

part_of

GO:0005887: integral component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CD47

acts_upstream_of_or_within

GO:0008228: opsonization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CD47

acts_upstream_of_or_within

GO:0050766: positive regulation of phagocytosis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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