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Developmental, Malignancy-Related, and Cross-Species Analysis of Eosinophil, Mast Cell, and Basophil Siglec-8 Expression

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Abstract

Objective

The aim of this study is to determine when during hematopoiesis Siglec-8 gets expressed, whether it is expressed on hematologic malignancies, and if there are other non-human species that express Siglec-8.

Methods

Siglec-8 mRNA and cell surface expression was monitored during in vitro maturation of human eosinophils and mast cells. Flow cytometry was performed on human blood and bone marrow samples, and on blood samples from dogs, baboons, and rhesus and cynomolgus monkeys.

Results

Siglec-8 is a late maturation marker. It is detectable on eosinophils and basophils from subjects with chronic eosinophilic leukemia, chronic myelogenous leukemia, and on malignant and non-malignant bone marrow mast cells, as well as the HMC-1.2 cell line. None of the Siglec-8 monoclonal antibodies tested recognized leukocytes from dogs, baboons, and rhesus and cynomolgus monkeys.

Conclusions

Siglec-8-based therapies should not target immature human leukocytes but should recognize mature and malignant eosinophils, mast cells, and basophils. So far, there is no suitable species for preclinical testing of Siglec-8 monoclonal antibodies.

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References

  1. Floyd H, Ni J, Cornish AL, Zeng Z, Liu D, Carter KC, et al. Siglec-8: a novel eosinophil-specific member of the immunoglobulin superfamily. J Biol Chem. 2000;275:861–6.

    Article  PubMed  CAS  Google Scholar 

  2. Kikly KK, Bochner BS, Freeman S, Tan KB, Gallagher KT, D'Alessio K, et al. Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells and basophils. J Allergy Clin Immunol. 2000;105:1093–100.

    Article  PubMed  CAS  Google Scholar 

  3. Bochner BS. Siglec-8 on human eosinophils and mast cells, and Siglec-F on murine eosinophils, are functionally related inhibitory receptors. Clin Exp Allergy. 2009;39:317–24.

    Article  PubMed  CAS  Google Scholar 

  4. Hudson SA, Bovin N, Schnaar RL, Crocker PR, Bochner BS. Eosinophil-selective binding and pro-apoptotic effect in vitro of a synthetic Siglec-8 ligand, polymeric 6'-sulfated sialyl Lewis X. J Pharmacol Exp Ther. 2009;330:608–12.

    Article  PubMed  CAS  Google Scholar 

  5. Nutku E, Aizawa H, Hudson SA, Bochner BS. Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis. Blood. 2003;101:5014–20.

    Article  PubMed  CAS  Google Scholar 

  6. Nutku E, Hudson SA, Bochner BS. Mechanism of Siglec-8-induced human eosinophil apoptosis: role of caspases and mitochondrial injury. Biochem Biophys Res Commun. 2005;336:918–24.

    Article  PubMed  CAS  Google Scholar 

  7. Nutku-Bilir E, Hudson SA, Bochner BS. Interleukin-5 priming of human eosinophils alters Siglec-8 mediated apoptosis pathways. Am J Respir Cell Mol Biol. 2008;38:121–4.

    Article  PubMed  CAS  Google Scholar 

  8. Yokoi H, Choi OH, Hubbard W, Lee H-S, Canning BJ, Lee HH, et al. Inhibition of FcεRI-dependent mediator release and calcium flux from human mast cells by Siglec-8 engagement. J Allergy Clin Immunol. 2008;121:499–505.

    Article  PubMed  CAS  Google Scholar 

  9. Tateno H, Crocker PR, Paulson JC. Mouse Siglec-F and human Siglec-8 are functionally convergent paralogs that are selectively expressed on eosinophils and recognize 6'-sulfo-sialyl Lewis X as a preferred glycan ligand. Glycobiology. 2005;15:1125–35.

    Article  PubMed  CAS  Google Scholar 

  10. Varki A, Angata T. Siglecs—the major sub-family of I-type lectins. Glycobiology. 2006;16:1R–27R.

    Article  PubMed  CAS  Google Scholar 

  11. Cho JY, Song DJ, Pham A, Rosenthal P, Miller M, Dayan S, et al. Chronic OVA allergen challenged Siglec-F deficient mice have increased mucus, remodeling, and epithelial Siglec-F ligands which are up-regulated by IL-4 and IL-13. Respir Res. 2010;11:154.

    Article  PubMed  Google Scholar 

  12. Song DJ, Cho JY, Miller M, Strangman W, Zhang M, Varki A, et al. Anti-Siglec-F antibody inhibits oral egg allergen induced intestinal eosinophilic inflammation in a mouse model. Clin Immunol. 2009;131:157–69.

    Article  PubMed  CAS  Google Scholar 

  13. Song DJ, Cho JY, Lee SY, Miller M, Rosenthal P, Soroosh P, et al. Anti-Siglec-F antibody reduces allergen-induced eosinophilic inflammation and airway remodeling. J Immunol. 2009;183:5333–41.

    Article  PubMed  CAS  Google Scholar 

  14. Zimmermann N, McBride ML, Yamada Y, Hudson SA, Jones C, Cromie KD, et al. Siglec-F antibody administration to mice selectively reduces blood and tissue eosinophils. Allergy. 2008;63:1156–63.

    Article  PubMed  CAS  Google Scholar 

  15. Yokoi H, Myers A, Matsumoto K, Crocker PR, Saito H, Bochner BS. Alteration and acquisition of Siglecs during in vitro maturation of CD34+ progenitors into human mast cells. Allergy. 2006;61:769–76.

    Article  PubMed  CAS  Google Scholar 

  16. Dyer KD, Moser JM, Czapiga M, Siegel SJ, Percopo CM, Rosenberg HF. Functionally competent eosinophils differentiated ex vivo in high purity from normal mouse bone marrow. J Immunol. 2008;181:4004–9.

    PubMed  CAS  Google Scholar 

  17. Lilliehook I, Johannisson A, Hakansson L. Expression of adhesion and Fcγ-receptors on canine blood eosinophils and neutrophils studied by anti-human monoclonal antibodies. Vet Immunol Immunopathol. 1998;61:181–93.

    Article  PubMed  CAS  Google Scholar 

  18. Bedi R, Du J, Sharma AK, Gomes I, Ackerman SJ. Human C/EBP-epsilon activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation. Blood. 2009;113:317–27.

    Article  PubMed  CAS  Google Scholar 

  19. Mirkina I, Schweighoffer T, Kricek F. Inhibition of human cord blood-derived mast cell responses by anti-FcεRI mAb 15/1 versus anti-IgE omalizumab. Immunol Lett. 2007;109:120–8.

    Article  PubMed  CAS  Google Scholar 

  20. Aichberger KJ, Gleixner KV, Mirkina I, Cerny-Reiterer S, Peter B, Ferenc V, et al. Identification of proapoptotic Bim as a tumor suppressor in neoplastic mast cells: role of KIT D816V and effects of various targeted drugs. Blood. 2009;114:5342–51.

    Article  PubMed  CAS  Google Scholar 

  21. Baumann MA, Paul CC. The AML14 and AML14.3D10 cell lines: a long-overdue model for the study of eosinophils and more. Stem Cells. 1998;16:16–24.

    Article  PubMed  CAS  Google Scholar 

  22. Du J, Stankiewicz MJ, Liu Y, Xi Q, Schmitz JE, Lekstrom-Himes JA, et al. Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein. J Biol Chem. 2002;277:43481–94.

    Article  PubMed  CAS  Google Scholar 

  23. Du J, Alsayed YM, Xin F, Ackerman SJ, Platanias LC. Engagement of the CrkL adapter in interleukin-5 signaling in eosinophils. J Biol Chem. 2000;275:33167–75.

    Article  PubMed  CAS  Google Scholar 

  24. Vardiman J, Melo J, Baccarani M, Thiele J. Chronic myelogenous leukemia, BCR/ABL1 positive. In: Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, et al., editors. World Health Organization (WHO) classification of tumours pathology & genetics tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2008. p. 32–7.

    Google Scholar 

  25. Ellis AK, Ackerman SJ, Crawford L, Du J, Bedi R, Denburg JA. Cord blood molecular biomarkers of eosinophilopoiesis: kinetic analysis of GATA-1, MBP1 and IL-5R alpha mRNA expression. Pediatr Allergy Immunol. 2010;21:640–8.

    Article  PubMed  Google Scholar 

  26. Mayerhofer M, Gleixner KV, Hoelbl A, Florian S, Hoermann G, Aichberger KJ, et al. Unique effects of KIT D816V in BaF3 cells: induction of cluster formation, histamine synthesis, and early mast cell differentiation antigens. J Immunol. 2008;180:5466–76.

    PubMed  CAS  Google Scholar 

  27. Angata T, Hingorani R, Varki NM, Varki A. Cloning and characterization of a novel mouse Siglec, mSiglec-F: differential evolution of the mouse and human (CD33) Siglec-3-related gene clusters. J Biol Chem. 2001;276:45128–36.

    Article  PubMed  CAS  Google Scholar 

  28. Angata T, Margulies EH, Green ED, Varki A. Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanisms. Proc Natl Acad Sci USA. 2004;101:13251–6.

    Article  PubMed  CAS  Google Scholar 

  29. Cao H, de Bono B, Belov K, Wong ES, Trowsdale J, Barrow AD. Comparative genomics indicates the mammalian CD33rSiglec locus evolved by an ancient large-scale inverse duplication and suggests all Siglecs share a common ancestral region. Immunogenetics. 2009;61:401–17.

    Article  PubMed  CAS  Google Scholar 

  30. O'Reilly MK, Paulson JC. Siglecs as targets for therapy in immune-cell-mediated disease. Trends Pharmacol Sci. 2009;30:240–8.

    Article  PubMed  Google Scholar 

  31. Chen WC, Completo GC, Sigal DS, Crocker PR, Saven A, Paulson JC. In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood. 2010;115:4778–86.

    Article  PubMed  CAS  Google Scholar 

  32. Kardava L, Moir S, Wang W, Ho J, Buckner CM, Posada JG, et al. Attenuation of HIV-associated human B cell exhaustion by siRNA downregulation of inhibitory receptors. J Clin Invest. 2011;121:2614–24.

    Article  PubMed  CAS  Google Scholar 

  33. von Gunten S, Bochner BS. Expression and function of Siglec-8 in human eosinophils, basophils and mast cells. In: Pawankar R, Holgate S, Rosenwasser LJ, editors. Allergy frontiers: classification and pathomechanisms. Tokyo: Springer; 2009. p. 297–313.

    Chapter  Google Scholar 

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Acknowledgments

The authors thank Warren Gold, Cassandra Paul, Michael Baumann, and Joseph Butterfield for generously providing cell lines used in this paper. We also thank Joe Chrest for assistance with cell sorting.

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Sherry A. Hudson & Bruce S. Bochner

  2. Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria

    Harald Herrmann & Peter Valent

  3. Departments of Biochemistry and Molecular Genetics, and Medicine—Section of Hematology Oncology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Jian Du & Steven J. Ackerman

  4. Sanofi-Aventis US, LLC, Bridgewater, NJ, USA

    Paul Cox, El-Bdaoui Haddad & Barbara Butler

  5. Division of Cell Biology and Immunology, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee, UK

    Paul R. Crocker

  6. Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD, 21224-6821, USA

    Bruce S. Bochner

Authors
  1. Sherry A. Hudson
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  2. Harald Herrmann
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  10. Bruce S. Bochner
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Corresponding author

Correspondence to Bruce S. Bochner.

Additional information

Supported in part by grants from the National Institutes of Health (AI41472 and AI72265 to BSB), by the Fonds zur Förderung der Wissenschaftlichen Forschung in Österreich (SFB #018-20 to PV), the Campaign Urging Research on Eosinophilic Diseases (CURED, to SJA), and a pilot grant (to SJA) from The University of Illinois at Chicago (UIC) Center for Clinical and Translational Science (CCTS), Award Number UL1RR029879 from the National Center For Research Resources. The work of the Center is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health. Dr. Bochner also received support as a Cosner Scholar in Translational Research from The Johns Hopkins University School of Medicine, and is a co-author on existing and pending Siglec-8-related patents. If Siglec-8-related products are developed in the future, Dr. Bochner may be entitled to a share of royalties received by The Johns Hopkins University on the potential sales of such products. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.

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Hudson, S.A., Herrmann, H., Du, J. et al. Developmental, Malignancy-Related, and Cross-Species Analysis of Eosinophil, Mast Cell, and Basophil Siglec-8 Expression. J Clin Immunol 31, 1045–1053 (2011). https://doi.org/10.1007/s10875-011-9589-4

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  • DOI: https://doi.org/10.1007/s10875-011-9589-4

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