Role of CD47 as a Marker of Self on Red Blood Cells

Oldenborg, Per‐Arne; Zheleznyak, Alex; Fang, Yifu; Lagenaur, Carl F.; Gresham, Hattie D.; Lindberg, Frederik P.

doi:10.1126/science.288.5473.2051

Cited by 1,539 publications

(1,522 citation statements)

References 23 publications

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“…Red blood cells from CD47 knockout mice are cleared rapidly when transferred to wild type mice which is compatible with CD47 giving an inhibitory signal to phagocytic SIRPα positive cells [30]. However this result raises questions as to why this CD47−/− mouse does not eat its own blood cells and become non-viable?…”

Section: When Are Interactions Between Sirpα and Cd47 Functional? Effmentioning

confidence: 89%

Signal regulatory protein alpha (SIRPα)/CD47 interaction and function

Barclay

2009

Current Opinion in Immunology

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SummarySIRPα is an inhibitory receptor present on myeloid cells that interacts with a widely distributed membrane protein CD47. The activating member SIRPβ, despite extensive sequence similarity to SIRPα in the extracellular region, shows negligible binding to CD47. The SIRPα / CD47 interaction is unusual in that it can lead to bidirectional signalling through both SIRPα and CD47. This review concentrates on the interactions of SIRPα with CD47 where recent data have shed light on the structure of the proteins including determining why the activating SIRPβ does not bind CD47, evidence of extensive polymorphisms and implication for the evolution and function of this protein and paired receptors in general. The interaction may be modified by endocytosis of the receptors, cleavage by proteolysis and through interactions of surfactant proteins.

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Section: When Are Interactions Between Sirpα and Cd47 Functional? Effmentioning

confidence: 89%

Signal regulatory protein alpha (SIRPα)/CD47 interaction and function

Barclay

2009

Current Opinion in Immunology

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“…5,6 CD47 interacts with signal regulatory protein-a (SIRPa), thrombospondin (TSP)-1 and -2 to mediate various cellular functions. 7,8 In particular, CD47 signaling through SIRPa inhibits the phagocytosis of CD47-expressing target cells by SIRPa-expressing macrophages.…”

Section: Introductionmentioning

confidence: 99%

Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells

et al. 2012

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Multiple myeloma is a plasma cell neoplasm residing in bone marrow. Despite advances in myeloma therapies, novel therapies are required to improve patient outcomes. CD47 is highly expressed on myeloma cells and a potential therapeutic candidate for myeloma therapies. Flow cytometric analysis of patient bone marrow cells revealed that myeloma cells overexpress CD47 when compared with non-myeloma cells in 73% of patients (27/37). CD47 expression protects cells from phagocytosis by transmitting an inhibitory signal to macrophages. Here we show that blocking CD47 with an anti-CD47 monoclonal antibody increased phagocytosis of myeloma cells in vitro. In xenotransplantation models, anti-CD47 antibodies inhibited the growth of RPMI 8226 myeloma cells and led to tumor regression (42/57 mice), implicating the eradication of myeloma-initiating cells. Moreover, anti-CD47 antibodies retarded the growth of patient myeloma cells and alleviated bone resorption in human bone-bearing mice. Irradiation of mice before myeloma cell xenotransplantation abolished the therapeutic efficacy of anti-CD47 antibodies delivered 2 weeks after radiation, and coincided with a reduction of myelomonocytic cells in spleen, bone marrow and liver. These results are consistent with the hypothesis that anti-CD47 blocking antibodies inhibit myeloma growth, in part, by increasing phagocytosis of myeloma cells.

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“…The CD47-SHPS-1 system has been shown to regulate a novel cell-cell communication system that is important in immunology and hematology. CD47 on red blood cells binds to SHPS-1 on macrophages, thereby inhibiting macrophage activation and phagocytosis [28,29]. The interaction of SHPS-1 with CD47 negatively regulates cellular responsiveness during T cell activation and during the induction of antigen-specific cytotoxic T lymphocytes by DC and monocytes [24,30].…”

mentioning

confidence: 99%

Src homology 2 domain‐containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation

Fukunaga

Nagai

et al. 2006

Eur J Immunol

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Recently, we reported that Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1) plays an important role in the migration of Langerhans cells (LC). Here, we show that SHPS-1 is involved in the maturation of LC. Immunofluorescence analysis on epidermal sheets for I-A or CD86 revealed that LC maturation induced by 2,4-dinitro-1-fluorobenzene (DNFB) or by TNF-a was inhibited by pretreatment with an anti-SHPS-1 monoclonal antibody (mAb) or with CD47-Fc fusion protein, a ligand for SHPS-1. Further, FACS analysis demonstrated that I-A + LC that had emigrated from skin explants expressed CD80 or CD86, whereas CD47-Fc protein reduced CD80 high+ or CD86 high+ cells. CD47-Fc protein also reduced the upregulation of surface CD80 or CD86 by LC remaining in the skin explants. In SHPS-1 mutant mice, we observed that the up-regulation of surface CD86 and CCR7 by LC induced by DNFB as well as that of surface CD80 and CD86 by LC in skin explants was attenuated. Finally, contact hypersensitivity (CHS) response was suppressed in SHPS-1 mutant mice and in wild-type mice treated with an anti-SHPS-1 mAb. These observations indicate that SHPS-1 plays an important role in the maturation of LC ex vivo and in vivo, and that SHPS-1-CD47 interaction may negatively regulate CHS. IntroductionDC are potent antigen-presenting cells that play a crucial role in the initiation of immune responses to pathogens. Langerhans cells (LC) are specialized immature DC in the skin that reside in the suprabasal layers of the epidermis. When LC encounter exogenous antigens, including haptens and microorganisms, they capture and process them to generate MHC/peptide complexes on their surface. LC migrate from the epidermis to draining lymphoid tissues in order to initiate naive T cells and to present the MHC/peptide complexes to Correspondence: Dr. Tatsuya Horikawa, Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017Japan Fax:+81-78-382-6149 e-mail: thorikaw@med.kobe-u.ac.jp Received 12/1/06Revised 13/9/06 Accepted 19/10/06 [DOI 10.1002/eji.200635864] Key words: Contact hypersensitivity Á Langerhans cells Á Maturation Á Src homology 2 domaincontaining protein tyrosine phosphatase substrate 1Abbreviations: CCR7: CC chemokine receptor 7 Á CHS: contact hypersensitivity Á DNFB: 2,4-dinitro-1-fluorobenzene Á LC: Langerhans cell Á SHPS-1: Src homology 2 domaincontaining protein tyrosine phosphatase substrate 1 Á SIRP a1: signal-regulatory protein a1 and . In mice, SHPS-1 is expressed in myeloid cells, including monocytes, macrophages and DC [25]. SHPS-1 is a transmembrane glycoprotein whose extracellular domain comprises three immunoglobulin-like domains with multiple N-linked glycosylation sites, while the cytoplasmic domain of SHPS-1 contains four tyrosine residues that form two ITIM [26]. SHPS-1 was initially discovered as a tyrosine-phosphorylated transmembrane protein that binds SHP-1 or SHP-2. IAP/CD47, an integrin-associated...

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Role of CD47 as a Marker of Self on Red Blood Cells

Cited by 1,539 publications

References 23 publications

Signal regulatory protein alpha (SIRPα)/CD47 interaction and function

Signal regulatory protein alpha (SIRPα)/CD47 interaction and function

Anti-CD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells

Src homology 2 domain‐containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation

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