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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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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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  3. Jian Du
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  4. Paul Cox
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  7. Paul R. Crocker
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  8. Steven J. Ackerman
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  9. Peter Valent
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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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