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

Barclay, A. Neil

doi:10.1016/j.coi.2009.01.008

Cited by 101 publications

(97 citation statements)

References 41 publications

(53 reference statements)

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“…CD47 is recognized as a checkpoint for the innate immune response and delivers an inhibitory signal when it binds with SIRPα expressed on phagocytes (30)(31)(32). Anti-CD47 treat-30-32).…”

Section: Discussionmentioning

confidence: 99%

Characterization of cluster of differentiationï¿½47 expression and its potential as a therapeutic target in esophageal squamous cell cancer

Zhao

Wang

et al. 2017

Oncol Lett

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Abstract. The increased expression of cluster of differentiation (CD)47 has been identified in a number of different tumor types and is recognized as an adverse prognostic factor that indicates an increased risk of mortality in patients. The binding of CD47 to signal regulatory protein α (SIRPα) inhibits the macrophage phagocytosis of tumor cells by triggering an inhibitory 'do not eat me' signal. This is one of the mechanisms used by tumor cells to evade immune surveillance. In the present study, CD47 levels and macrophage infiltration were assessed in patients with esophageal squamous cell cancer (ESCC). CD47-overexpressing ESCC cell lines were selected and human M2 macrophage phagocytic activity was measured. The results revealed that CD47 is highly expressed and macrophages are markedly infiltrated in cancerous tissue compared with non-cancerous tissue. High CD47 expression was detected in ESCC cell lines and the results of a phagocytosis assay indicated that human M2 macrophages phagocytized tumor cells in a dose-dependent manner following the blocking of CD47-SIRPα signaling by anti-CD47 antibodies. The results of the present study therefore support the use of anti-CD47 immunotherapy to treat patients with ESCC.

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“…CD47 is recognized as a checkpoint for the innate immune response and delivers an inhibitory signal when it binds with SIRPα expressed on phagocytes (30)(31)(32). Anti-CD47 treat-30-32).…”

Section: Discussionmentioning

confidence: 99%

Characterization of cluster of differentiationï¿½47 expression and its potential as a therapeutic target in esophageal squamous cell cancer

Zhao

Wang

et al. 2017

Oncol Lett

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“…The resulting complexity of CD47 biology may explain its broad-but not fully elucidated-role in hematopoietic and immune processes. The expression pattern of SIRPα is restricted to neuronal and hematopoietic lineages, with a remarkable bias to immune cells exhibiting a phagocytic activity (e.g., macrophages, granulocytes, or dendritic cells) (19). CD47 null mice are viable and apparently healthy; however, phenotypic differences with their CD47 + littermates are revealed in a pathogenic setting, because CD47 −/− mice are unable to control Escherichia coli bacterial infection (22).…”

mentioning

confidence: 99%

“…Phagocyte activity is inhibited by interactions between CD47 and signal regulatory protein alpha (SIRPα; CD172a) (19). CD47, a ubiquitously expressed Ig-like membrane protein, can interact with several other cell surface receptors (e.g., thrombospondin, integrins, and other members of the SIRP family) (20).…”

mentioning

confidence: 99%

Functional CD47/signal regulatory protein alpha (SIRPα) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo

Legrand

Huntington

Nagasawa

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

169

155

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The homeostatic control mechanisms regulating human leukocyte numbers are poorly understood. Here, we assessed the role of phagocytes in this process using human immune system (HIS) BALB/c Rag2 −/− IL-2Rγc −/− mice in which human leukocytes are generated from transplanted hematopoietic progenitor cells. Interactions between signal regulatory protein alpha (SIRPα; expressed on phagocytes) and CD47 (expressed on hematopoietic cells) negatively regulate phagocyte activity of macrophages and other phagocytic cells. We previously showed that B cells develop and survive robustly in HIS mice, whereas T and natural killer (NK) cells survive poorly. Because human CD47 does not interact with BALB/c mouse SIRPα, we introduced functional CD47/SIRPα interactions in HIS mice by transducing mouse CD47 into human progenitor cells. Here, we show that this procedure resulted in a dramatic and selective improvement of progenitor cell engraftment and human T-and NK-cell homeostasis in HIS mouse peripheral lymphoid organs. The amount of engrafted human B cells also increased but much less than that of T and NK cells, and total plasma IgM and IgG concentrations increased 68-and 35-fold, respectively. Whereas T cells exhibit an activated/memory phenotype in the absence of functional CD47/SIRPα interactions, human T cells accumulated as CD4 + or CD8 + single-positive, naive, resting T cells in the presence of functional CD47/SIRPα interactions. Thus, in addition to signals mediated by T cell receptor (TCR)/MHC and/or IL/IL receptor interactions, sensing of cell surface CD47 expression by phagocyte SIRPα is a critical determinant of T-and NK-cell homeostasis under steady-state conditions in vivo.hematopoiesis | humanized mice | leukocyte homeostasis

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“…CD47 is a receptor for the C-terminal cell binding domain of thrombospondin-1 (TSP-1) and a ligand for the extracellular region of signal-regulatory protein alpha (SIRPα) [41] . CD47 is ubiquitously expressed on human cells and involved in many fundamental cellular processes including immune and angiogenic responses [40] .…”

Section: Cd47mentioning

confidence: 99%

Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

Zhou

Chng

2014

WJSC

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Accumulating evidence support the notion that acute myeloid leukemia (AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells (LSC). Similar to their normal counterpart, hematopoietic stem cells (HSC), LSC possess selfrenewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normal HSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC.

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

Cited by 101 publications

References 41 publications

Characterization of cluster of differentiationï¿½47 expression and its potential as a therapeutic target in esophageal squamous cell cancer

Characterization of cluster of differentiationï¿½47 expression and its potential as a therapeutic target in esophageal squamous cell cancer

Functional CD47/signal regulatory protein alpha (SIRPα) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo

Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

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