Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells, and basophils

Kikly, Kristine; Bochner, Bruce S.; Freeman, Sylvie; Tan, K. B.; Gallagher, Kathleen T.; D'Alessio, Karla; Holmes, Stephen D.; Abrahamson, Julie A.; Erickson‐Miller, Connie L.; Murdock, Paul R.; Tachimoto, Hiroshi; Schleimer, Robert P.; White, John R.

doi:10.1067/mai.2000.107127

Cited by 147 publications

(148 citation statements)

References 35 publications

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“…In BM, we observed that also CCR3 dim cells, which according to studies in mice may represent immature eosinophils [19], were EMR1 + . Notably, while CCR3 and Siglec-8 are also expressed by basophils [20,21], EMR1 was absent on basophils and thus is a highly specific marker for eosinophils in humans (Fig. 2E, Table 1).…”

Section: Eosinophilic Granulocytes Express Emr1mentioning

confidence: 99%

EMR1, the human homolog of F4/80, is an eosinophil‐specific receptor

et al. 2007

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The EGF-TM7 F4/80 is a defining marker of murine macrophage populations. Applying flow cytometric analysis using the newly generated mAb A10, and quantitative real-time PCR, we here report the surprising observation that the human ortholog of F4/80, EGFlike module containing mucin-like hormone receptor (EMR)1, is absent on mononuclear phagocytic cells including monocytes, macrophages, and myeloid dendritic cells. Unexpectedly, we found that EMR1 expression is restricted to eosinophilic granulocytes, where expression is overlapping with the eotaxin receptor CCR3 and the immunoglobulin-like lectin Siglec-8. Absence on other leukocytes, including basophils, implies that EMR1 is a highly specific marker for eosinophils in humans.

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Section: Eosinophilic Granulocytes Express Emr1mentioning

confidence: 99%

EMR1, the human homolog of F4/80, is an eosinophil‐specific receptor

et al. 2007

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“…19 Of interest, this structure is also the preferred ligand for human Siglec-8, 20 a molecule also specifically expressed on human eosinophils. 21,22 Although mouse Siglec-F is not the true ortholog of human Siglec-8, 18 their marked similarities in expression patterns and ligand preferences suggest that they play equivalent roles. Studying Siglec-F in a mouse model should therefore provide general insights into the currently unknown biologic roles of typical CD33rSiglecs with ITIMs, as well as about the physiological functions of Siglec-8 in human eosinophils, and in eosinophilmediated diseases.…”

Section: Introductionmentioning

confidence: 99%

Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils

Zhang

Angata

Cho

et al. 2007

Blood

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CD33-related Siglecs (CD33rSiglecs) are a family of sialic acid–recognizing lectins on immune cells whose biologic functions are unknown. We studied in vivo functions of Siglec-F, the CD33rSiglec expressed on mouse eosinophils, which are prominent in allergic processes. Induction of allergic lung inflammation in mice caused up-regulation of Siglec-F on blood and bone marrow eosinophils, accompanied by newly induced expression on some CD4+ cells, as well as quantitative up-regulation of endogenous Siglec-F ligands in the lung tissue and airways. Taken together with the tyrosine-based inhibitory motif in the cytosolic tail of Siglec-F, the data suggested a negative feedback loop, controlling allergic responses of eosinophils and helper T cells, via Siglec-F and Siglec-F ligands. To pursue this hypothesis, we created Siglec-F–null mice. Allergen-challenged null mice showed increased lung eosinophil infiltration, enhanced bone marrow and blood eosinophilia, delayed resolution of lung eosinophilia, and reduced peribronchial-cell apoptosis. Anti–Siglec-F antibody cross-linking also enhanced eosinophil apoptosis in vitro. These data support the proposed negative feedback role for Siglec-F, represent the first in vivo demonstration of biologic functions for any CD33rSiglec, and predict a role for human Siglec-8 (the isofunctional paralog of mouse Siglec-F) in regulating the pathogenesis of human eosinophil-mediated disorders.

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“…2 It has been demonstrated that Siglec-8 engagement induces eosinophil apoptosis in vitro by triggering the 'intrinsic' stressmediated apoptotic pathway through sequential ROS production, mitochondrial dysfunction, and caspase cleavage. 3 Of interest, murine Siglec-8 variations and asthma P-S Gao et al studies targeting Siglec-F, the closest functional paralog to Siglec-8, also demonstrated a significant role in regulating the pathogenesis of eosinophil-mediated disorders.…”

Section: Discussionmentioning

confidence: 99%

“…1 Siglec-8 is a type-I transmembrane protein expressed on human eosinophils, mast cells, and basophils. 2,3 This transmembrane protein has an extracellular binding domain that recognizes specific complex carbohydrates (glycans such as 6¢-sulfated sialyl Lewis X (6¢-sulfo-sLe x )), 4 and intracellular immunoreceptor tyrosine-based inhibition motifs (ITIMs) that facilitate receptor binding into inhibitory signals. We have reported that incubation of human eosinophils with specific Siglec-8 monoclonal antibodies (mAbs) causes rapid caspaseand ROS-dependent apoptosis [5][6][7] This was further supported by studies using mouse Siglec-F, the closest functional paralog of human showing that Siglec-F engagement on murine eosinophils by antibodies induces their apoptosis in vitro, and administration of Siglec-F antibodies to hyper-eosinophilic mice reduces circulating and tissue eosinophils.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma

et al. 2010

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Sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) promotes the apoptosis of eosinophils and inhibits FceRI-dependent mediator release from mast cells. We investigated the genetic association between sequence variants in Siglec-8 and diagnosis of asthma, total levels of serum IgE (tIgE), and diagnosis of eosinophilic esophagitis (EE) in diverse populations. The effect of sequence variants on Siglec-8 glycan ligand-binding activity was also examined. Significant association with asthma was observed for SNP rs36498 (odds ratios (OR), 0.69, P¼8.8Â10 À5 ) among African Americans and for SNP rs10409962 (Ser/Pro) in the Japanese population (OR, 0.69, P¼0.019). Supporting this finding, we observed association between SNP rs36498 and current asthma among Brazilian families (P¼0.013). Significant association with tIgE was observed for SNP rs6509541 among African Americans (P¼0.016), and replicated among the Brazilian families (P¼0.02). In contrast, no association was observed with EE in Caucasians. By using a synthetic polymer decorated with 6¢-sulfo-sLe x , a known Siglec-8 glycan ligand, we did not find any differences between the ligand-binding activity of HEK293 cells stably transfected with the rs10409962 risk allele or the WT allele. However, our association results suggest that the Siglec8 gene may be a susceptibility locus for asthma.

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Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells, and basophils

Cited by 147 publications

References 35 publications

EMR1, the human homolog of F4/80, is an eosinophil‐specific receptor

EMR1, the human homolog of F4/80, is an eosinophil‐specific receptor

Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils

Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma

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