Tethering of apoptotic cells to phagocytes through binding of CD47 to Src homology 2 domain-bearing protein tyrosine phosphatase substrate-1.
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.
Tada
Kazutoshi
K
Department of Genetics, Osaka University Medical School, Osaka, Japan.
Tanaka
Masato
M
Hanayama
Rikinari
R
Miwa
Keiko
K
Shinohara
Azusa
A
Iwamatsu
Akihiro
A
Nagata
Shigekazu
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D000943:Antigens, Differentiation; D017209:Apoptosis / Q000276:immunology*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D039842:Neural Cell Adhesion Molecule L1 / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D010586:Phagocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology*; D010718:Phosphatidylserines / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011971:Receptors, Immunologic; D013379:Substrate Specificity / Q000276:immunology; D018909:src Homology Domains / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; C497895:Cd47 protein, mouse; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D010718:Phosphatidylserines; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D017027:Protein Tyrosine Phosphatases