Top

Published in:

01-12-2011

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

Authors: Sherry A. Hudson, Harald Herrmann, Jian Du, Paul Cox, El-Bdaoui Haddad, Barbara Butler, Paul R. Crocker, Steven J. Ackerman, Peter Valent, Bruce S. Bochner

Published in: Journal of Clinical Immunology | Issue 6/2011

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.

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

10.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.

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.PubMedCrossRef

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

30.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.CrossRef

Title: Developmental, Malignancy-Related, and Cross-Species Analysis of Eosinophil, Mast Cell, and Basophil Siglec-8 Expression
Authors: Sherry A. Hudson
Harald Herrmann
Jian Du
Paul Cox
El-Bdaoui Haddad
Barbara Butler
Paul R. Crocker
Steven J. Ackerman
Peter Valent
Bruce S. Bochner
Publication date: 01-12-2011
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 6/2011
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-011-9589-4

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Objective

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2011

A Prospective Study of Influenza Vaccination and a Comparison of Immunologic Parameters in Children and Adults with Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome)

Tyrosine Kinase Inhibitors Ameliorate Autoimmune Encephalomyelitis in a Mouse Model of Multiple Sclerosis

Altered Phenotype and Functionality of Circulating Immune Cells Characterize Adult Patients with Nonalcoholic Steatohepatitis

IL-9 Contributes to Immunosuppression Mediated by Regulatory T Cells and Mast Cells in B-Cell Non-Hodgkin’s Lymphoma

Kinetics of Effector Functions and Phenotype of Virus-Specific and γδ T Lymphocytes in Primary Human Cytomegalovirus Infection During Pregnancy

Nationwide Survey of Patients with Primary Immunodeficiency Diseases in Japan

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page