CD47 is a ligand for rat macrophage membrane signal regulatory protein SIRP (OX41) and human SIRPα 1

Vernon-Wilson, Elizabeth; Kee, Wai-Jing; Willis, Antony C.; Barclay, A. Neil; Simmons, David L.; Brown, Marion H.

doi:10.1002/1521-4141(2000)30:8<2130::aid-immu2130>3.0.co;2-8

Cited by 110 publications

(108 citation statements)

References 28 publications

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“…The mapping of the binding site on domain 1 of CD200R together with the complementary data for CD200 itself [13] shows that the CD200/ CD200R interaction also spans this distance providing evidence for areas of close contact between myeloid and other cells in addition to the 'classical' synapse described for T cell interactions [2,11]. Interactions between the membrane proteins of myeloid and cells other than lymphocytes are less well characterized than those of T cells and dendritic cells, but it is notable that the CD47/signal regulatory protein (SIRP) § interaction also spans four IgSF domains although in this case the SIRP § contains three domains and CD47 one domain [20].…”

Section: Discussionmentioning

confidence: 99%

The CD200 and CD200 receptor cell surface proteins interact through their N‐terminal immunoglobulin‐like domains

Hatherley

Barclay

2004

Eur J Immunol

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CD200 (OX2) is a broadly distributed cell surface glycoprotein that interacts with a receptor on myeloid cells (CD200R) involved in regulation of macrophage function. Both CD200 and CD200R contain two Ig superfamily domains like many other leukocyte membrane proteins. Site‐directed mutagenesis of CD200R showed that, like CD200, it interacted through its N‐terminal domain. This indicated that the cell‐cell interaction spans four Ig superfamily domains and this distance is similar to many interactions found between T cells and antigen‐presenting cells. This suggests that this topology is also important in interactions of CD200 on a variety of cells with CD200R on myeloid cells, and comparable contact sites may be important mediating regulation in other cell‐cell interactions. The mutagenesis showed that the binding involved the predicted GFCC′ face of its N‐terminal domain, like that of CD200, suggesting that the interaction evolved from a homotypic interaction.

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Section: Discussionmentioning

confidence: 99%

The CD200 and CD200 receptor cell surface proteins interact through their N‐terminal immunoglobulin‐like domains

Hatherley

Barclay

2004

Eur J Immunol

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“…With CD47 on the target, activation of the SIRP ␣ → SHP-1 phosphatase pathway ( Vernon-Wilson et al, 2000 ) could in principle block engulfment by regulating various kinase or phosphatase activities (such as Cbl) or perhaps even by regulating signaling to NMM IIA. Our immunoblot analysis followed by LC-MS/MS indeed identifi ed direct phosphorylation of Y 1805 in this myosin ' s self-assembling tail as an ultimate target for CD47-SIRP ␣ interaction.…”

Section: Chemicalsmentioning

confidence: 99%

“…Plasmids encoding the extracellular domain of human CD47 were PCR amplifi ed, digested with XbaI and SalI (New England Biolabs, Inc.), and ligated to similarly digested vector, pEF-BOS-XB ( Vernon-Wilson et al, 2000 ), which results in an in-frame fusion of CD4d3 + 4-biotin at the C terminus of the extracellular domain of CD47. The above vector containing the extracellular domain of CD47 was transfected into CHO ( Ϫ K1) cells using Lipofectamine 2000 (Invitrogen).…”

Section: Production Of Recombinant Human Cd47mentioning

confidence: 99%

“…In contacts with human RBCs, however, the CD47-induced accumulation of SIRP ␣ at the synapse is expected to phospho-activate SIRP ␣ ' s immunoreceptor tyrosinebased inhibiting motif (ITIM) ( Kharitonenkov et al, 1997 ) with subsequent recruitment of inhibitory tyrosine phosphatases, particularly SHP-1 ( Tsuda et al, 1998 ;Veillette et al, 1998 ;Vernon-Wilson et al, 2000 ;Kant et al, 2002 ). Phosphatase activation is consistent with the relatively large and dominant decrease found here for phosphotyrosine.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells

Tsai¹,

Discher²

2008

J Exp Med

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(2008). Inhibition of "self " engulfment through deactivation of myosin-II at the phagocytic synapse between human cells. Retrieved from http://repository.upenn.edu/cbe_papers/108Inhibition of "self " engulfment through deactivation of myosin-II at the phagocytic synapse between human cells AbstractPhagocytosis of foreign cells or particles by macrophages is a rapid process that is inefficient when faced with "self " cells that display CD47-although signaling mechanisms in self-recognition have remained largely unknown. With human macrophages, we show the phagocytic synapse at cell contacts involves a basal level of actin-driven phagocytosis that, in the absence of species-specific CD47 signaling, is made more efficient by phospho-activated myosin. We use "foreign" sheep red blood cells (RBCs) together with CD47-blocked, antibody-opsonized human RBCs in order to visualize synaptic accumulation of phosphotyrosine, paxillin, Factin, and the major motor isoform, nonmuscle myosin-IIA. When CD47 is functional, the macrophage counter-receptor and phosphatase-activator SIRPα localizes to the synapse, suppressing accumulation of phosphotyrosine and myosin without affecting F-actin. On both RBCs and microbeads, human CD47 potently inhibits phagocytosis as does direct inhibition of myosin. CD47-SIRPα interaction initiates a dephosphorylation cascade directed in part at phosphotyrosine in myosin. A point mutation turns off this motor's contribution to phagocytosis, suggesting that self-recognition inhibits contractile engulfment. Comments

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“…CD47 on "self " red cells, platelets, lymphocytes, and other nonapoptotic cells inhibits clearance by macrophages in mice by signaling through SIRP␣ (13-16). However, in humans as opposed to mice, severe reductions of CD47 levels on red cells, as found on various Rh-deficient patient cells, can occur with little to no evidence of anemia or enhanced clearance by splenic macrophages (17, 18) and also little to no reported evidence of enhanced RBC interactions with peripheral blood monocytes (19).The single Ig domain of CD47 is sufficient for binding SIRP␣ at least for humans (20,21), but it may be significant that the human sequence of the lone Ig domain of CD47 differs from that of mice by 38% (Fig. 1A).…”

mentioning

confidence: 99%

Phylogenetic Divergence of CD47 Interactions with Human Signal Regulatory Protein α Reveals Locus of Species Specificity

Subramanian

Boder

Discher

2007

Journal of Biological Chemistry

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Cell-cell interactions between ubiquitously expressed integrinassociated protein (CD47) and its counterreceptor signal regulatory protein (SIRP␣) on phagocytes regulate a wide range of adhesive signaling processes, including the inhibition of phagocytosis as documented in mice. We show that CD47-SIRP␣ binding interactions are different between mice and humans, and we exploit phylogenetic divergence to identify the species-specific binding locus on the immunoglobulin domain of human CD47. All of the studies are conducted in the physiological context of membrane protein display on Chinese hamster ovary (CHO) cells. Novel quantitative flow cytometry analyses with CD47-green fluorescent protein and soluble human SIRP␣ as a probe show that neither human CD47 nor SIRP␣ requires glycosylation for interaction. Human CD47-expressing CHO cells spread rapidly on SIRP␣-coated glass surfaces, correlating well with the spreading of primary human T cells. In contrast, CHO cells expressing mouse CD47 spread minimally and show equally weak binding to soluble human SIRP␣. Further phylogenetic analyses and multisite substitutions of the CD47 Ig domain show that human to cow mutation of a cluster of seven residues on adjacent strands near the middle of the domain decreases the association constant for human SIRP␣ to about onethird that of human CD47. Direct tests of cell-cell adhesion between human monocytes and CD47-displaying CHO cells affirm the species specificity as well as the importance of the newly identified binding locus in cell-cell interactions.Cell-cell interactions are of course critical in immune function but can have important and revealing differences between species as well as nonlinear dependences on molecular parameters, such as affinity. We explore such general issues with integrin-associated protein (IAP), 2 or CD47, which is a ubiquitous but unique immunoglobulin superfamily receptor with a single Ig domain, a pentaspan transmembrane segment, and a variably spliced cytoplasmic tail (1). The known functional roles of CD47, originally limited to integrin activation (2), have expanded considerably since the identification of SIRP␣ as a physiological ligand (3-6). SIRP␣ is another Ig superfamily member with three Ig domains and a single span transmembrane segment. SIRP␣ is also broadly expressed, present at high levels on myeloid lineages (monocytes, neutrophils) and neurons but absent from many if not most other cells (7). Both CD47 and SIRP␣ are found in many mammals, but the differences in sequence (Fig. 1A) across species have yet to be evaluated. CD47-SIRP␣ interactions regulate transmigration of monocytes and neutrophils (8 -11) with severe impairment in neutrophil recruitment to sites of infection in CD47 knock-out mice (12). CD47 on "self " red cells, platelets, lymphocytes, and other nonapoptotic cells inhibits clearance by macrophages in mice by signaling through SIRP␣ (13-16). However, in humans as opposed to mice, severe reductions of CD47 levels on red cells, as found on various Rh-deficient patient ...

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CD47 is a ligand for rat macrophage membrane signal regulatory protein SIRP (OX41) and human SIRPα 1

Cited by 110 publications

References 28 publications

The CD200 and CD200 receptor cell surface proteins interact through their N‐terminal immunoglobulin‐like domains

The CD200 and CD200 receptor cell surface proteins interact through their N‐terminal immunoglobulin‐like domains

Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells

Phylogenetic Divergence of CD47 Interactions with Human Signal Regulatory Protein α Reveals Locus of Species Specificity

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