Cytokine effects of CD23 are mediated by an epitope distinct from the IgE binding site.

Mossalayi, M. Djavad; Arock, Michel; Delespesse, Guy; Hofstetter, H.; Bettler, Bernhard; Dalloul, Ali; Kilchherr, Erich; Quaaz, F; Debré, Patrice; Sarfati, M

doi:10.1002/j.1460-2075.1992.tb05531.x

Cited by 32 publications

(21 citation statements)

References 30 publications

(12 reference statements)

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“…Although there are pronounced differences between the structures derived by the two methods, both show a generally consistent overall structure for the C-type lectin head domain comprising eight ␤ sheets and two ␣ helices (14,15). The NMR structure reveals a striking distribution of acidic and basic residues on opposites faces of the lectin head domain and demonstrates unequivocally that the interaction surfaces for IgE and CD21 binding are spatially distinct (14); the data also support unequivocally earlier studies that suggested that these binding sites and the structures responsible for expression of cytokine-like activities are distinct (16). The crystal structure confirms that CD23 contains only a single calcium binding site in the lectin head and that conformational changes in the CD23 structure accompany calcium coordination in this site (15).…”

supporting

confidence: 82%

αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

Borland

Edkins

Acharya

et al. 2007

Journal of Biological Chemistry

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CD23 is a type II transmembrane glycoprotein synthesized by hematopoietic cells that has biological activity in both membrane-bound and freely soluble forms, acting via a number of receptors, including integrins. We demonstrate here that soluble CD23 (sCD23) sustains growth of human B cell precursors via an RGD-independent interaction with the ␣v␤5 integrin. The integrin recognizes a tripeptide motif in a small disulfidebonded loop at the N terminus of the lectin head region of CD23, centered around Arg 172 , Lys 173 , and Cys 174 (RKC). This RKC motif is present in all forms of sCD23 with cytokine-like activity, and cytokine activity is independent of the lectin head, an "inverse RGD" motif, and the CD21 and IgE binding sites. RKCcontaining peptides derived from this region of CD23 bind ␣v␤5 and are biologically active. The binding and activity of these peptides is unaffected by inclusion of a short peptide containing the classic RGD sequence recognized by integrins, and, in farWestern analyses, RKC-containing peptides bind to the ␤ subunit of the ␣v␤5 integrin. The interaction between ␣v␤5 and sCD23 indicates that integrins deliver to cells important signals initiated by soluble ligands without the requirement for interactions with RGD motifs in their common ligands. This mode of integrin signaling may not be restricted to ␣v␤5.CD23 is a 45-kDa type II transmembrane glycoprotein that functions as the low affinity receptor for IgE and negatively regulates IgE production by B lymphocytes (1-5). CD23 is cleaved by membrane-associated metalloproteases (6, 7) to yield soluble CD23 (sCD23) 6 proteins with molecular masses ranging from 37 to 16 kDa, all of which retain the capacity to regulate IgE synthesis; human sCD23 proteins exhibit pleiotropic cytokine-like activities (1-3). In the B cell compartment, sCD23 inhibits apoptosis of germinal center centrocytes and promotes their differentiation into plasmablasts (8), at least in part by binding to CD21 (9), and sCD23 also inhibits apoptosis in pre-B cell lines (10) through, as we report here, an interaction with the ␣v␤5 integrin. In association with interleukin-1␣, sCD23 promotes differentiation of monocytes and early thymocyte precursors (11) and, via binding to the ␣M␤2 (CD11b-CD18), ␣X␤2 (CD11c-CD18) (12), and ␣v␤3 integrins (13), stimulates tumor necrosis factor-␣ and interleukin-1␣ production by monocytes. The structures of the derCD23 protein, a naturally occurring sCD23 fragment generated by action of the derp1 protease from Dermatophagoides pteronyssinus, and of a 25-kDa sCD23 (residues 150 -321), have recently been solved by heteronuclear nuclear magnetic resonance spectroscopy (14) and x-ray crystallography (15), respectively. Although there are pronounced differences between the structures derived by the two methods, both show a generally consistent overall structure for the C-type lectin head domain comprising eight ␤ sheets and two ␣ helices (14, 15). The NMR structure reveals a striking distribution of acidic and basic residues on opposites faces of t...

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supporting

confidence: 82%

αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

Borland

Edkins

Acharya

et al. 2007

Journal of Biological Chemistry

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“…The C-terminal extracellular domain consists of a globular fold that has homology to the C-type lectin family (9). This globular domain has been shown to contain two distinct binding sites, one for IgE and a second that recognizes CD21 (complement receptor 2) (10,11). At the cell surface CD23 self-assembles to form homotrimers that have a higher affinity for IgE than the CD23 monomer (12,13).…”

Section: B-cells and Cells Of The Myeloid Lineage With Interleukin-4 mentioning

confidence: 99%

The Low Affinity IgE Receptor (CD23) Is Cleaved by the Metalloproteinase ADAM10

Lemieux

Blumenkron

Yeung

et al. 2007

Journal of Biological Chemistry

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The low affinity IgE receptor, Fc⑀RII (CD23), is both a positive and negative regulator of IgE synthesis. The proteinase activity that converts the membrane-bound form of CD23 into a soluble species (sCD23) is an important regulator of the function of CD23 and may be an important therapeutic target for the control of allergy and inflammation. We have characterized the catalytic activity of ADAM (a disintegrin and metalloproteinase) 10 toward human CD23. We found that ADAM10 efficiently catalyzes the cleavage of peptides derived from two distinct cleavage sites in the CD23 backbone. Tissue inhibitors of metalloproteinases and a specific prodomain-based inhibitor of ADAM10 perturb the release of endogenously produced CD23 from human leukemia cell lines as well as primary cultures of human B-cells. Expression of a mutant metalloproteinase-deficient construct of ADAM10 partially inhibited the production of sCD23. Similarly, small inhibitory RNA knockdown of ADAM10 partially inhibited CD23 release and resulted in the accumulation of the membrane-bound form of CD23 on the cells. ADAM10 contributes to CD23 shedding and thus could be considered a potential therapeutic target for the treatment of allergic disease.The low affinity IgE receptor Fc⑀RII (CD23) is a 46-kDa type II membrane protein that is expressed on B-cells and cells of the myeloid lineage (1). CD23 has multiple functions. It is both a positive and negative regulator of IgE synthesis (2). It facilitates IgE-dependent antigen presentation through its binding of IgEantigen complexes (3,4). Moreover, the release of proinflammmatory cytokines from macrophages is stimulated by CD23 binding to CD18/11b and /11c (complement receptors 3 and 4) (5-7).In humans, two isoforms of CD23 that differ by only seven amino acids in the short N-terminal cytoplasmic domain are observed (8). CD23a is expressed only on B-cells. Stimulation of B-cells and cells of the myeloid lineage with interleukin-4 (IL-4) 3 induces the expression of CD23b. The C-terminal extracellular domain consists of a globular fold that has homology to the C-type lectin family (9). This globular domain has been shown to contain two distinct binding sites, one for IgE and a second that recognizes CD21 (complement receptor 2) (10, 11). At the cell surface CD23 self-assembles to form homotrimers that have a higher affinity for IgE than the CD23 monomer (12, 13). The self-association is driven by a leucine zipper-like domain (14) that connects the N-terminal cytoplasmic and transmembrane domains to the C-terminal globular domain.Homotrimeric CD23 molecules exhibit a 15-nm ␣-helical coiled coil stalk that extends the globular C-terminal domains from the plasma membrane (15). Cleavage in the stalk region by a membrane-associated endoproteolytic activity generates soluble fragments of CD23 (sCD23) that possess apparent molecular masses of 37, 33, and 29 kDa (16). All three of these sCD23 fragments exist as homotrimers (15). Smaller fragments of CD23 (25 and 16 kDa) are known. However, these are thought to be form...

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“…In some experiments, supernatants of Chinese hamster ovary (CHO) cells producing various sCD23 fragments, including the 25-kDa fragments, were used. In this case, supernatants of CHO cells under the same culture conditions producing sCD23 3.90 mutant fragments served as controls [28].…”

Section: Cytokines and Scd23mentioning

confidence: 99%

“…hu rIL-6 was obtained from Janssen Biochemica (Beerse, Belgium). The purified source of human recombinant sCD23, the stable 25-kDa fragment, was a gift from M. D. Mossalayi (Laboratoire d'Immunologie, CHU Pitie-SalpCtriitre, Paris, France) [28]. In some experiments, supernatants of Chinese hamster ovary (CHO) cells producing various sCD23 fragments, including the 25-kDa fragments, were used.…”

Section: Cytokines and Scd23mentioning

confidence: 99%

Soluble CD23 potentiates interleukin‐1‐induced secretion of interleukin‐6 and interleukin‐1 receptor antagonist by human monocytes

Herbelin

Elhadadu

Ouaazu³

et al. 1994

Eur J Immunol

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The low-affinity receptor for IgE (CD23) is cleaved into biologically active soluble fragments (sCD23), some of which have been reported to exhibit pleiotropic activities. However, it is not known whether the sCD23 fragments contribute to the induction and/or regulation of pro-inflammatory cytokine production. In this study, this possibility was tested using interleukin (IL)-1-stimulated human whole blood as an ex vivo model of cytokine cascade production. We show that human recombinant 25-kDa sCD23 significantly enhanced the production of IL-6 in whole blood stimulated by IL-1, but had only little or no effect in the absence of IL-1. The potentiating effect of sCD23 was concentration dependent within the range of plasma levels occurring during various inflammatory processes in man. These results prompted us to study whether sCD23 and IL-1 together also enhance the production of regulating factors exhibiting anti-cytokine activities. Our data indicate that sCD23 augments the release of IL-1 receptor antagonist induced by IL-1. Finally, examining the effect of sCD23 on human peripheral monocytes stimulated by IL-1, we confirmed the capacity of sCD23 to potentiate cytokine production. We suggest that sCD23 can modulate monocyte functions, thereby contributing to the amplification and regulation of immune and inflammatory processes.

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Cytokine effects of CD23 are mediated by an epitope distinct from the IgE binding site.

Cited by 32 publications

References 30 publications

αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

αvβ5 Integrin Sustains Growth of Human Pre-B Cells through an RGD-independent Interaction with a Basic Domain of the CD23 Protein

The Low Affinity IgE Receptor (CD23) Is Cleaved by the Metalloproteinase ADAM10

Soluble CD23 potentiates interleukin‐1‐induced secretion of interleukin‐6 and interleukin‐1 receptor antagonist by human monocytes

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