Article

Journal of Clinical Immunology

, Volume 31, Issue 6, pp 1045-1053

First online:

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

  • Sherry A. HudsonAffiliated withDepartment of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine
  • , Harald HerrmannAffiliated withDepartment of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna
  • , Jian DuAffiliated withDepartments of Biochemistry and Molecular Genetics, and Medicine—Section of Hematology Oncology, College of Medicine, University of Illinois at Chicago
  • , Paul CoxAffiliated withSanofi-Aventis US, LLC
  • , El-Bdaoui HaddadAffiliated withSanofi-Aventis US, LLC
  • , Barbara ButlerAffiliated withSanofi-Aventis US, LLC
  • , Paul R. CrockerAffiliated withDivision of Cell Biology and Immunology, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee
  • , Steven J. AckermanAffiliated withDepartments of Biochemistry and Molecular Genetics, and Medicine—Section of Hematology Oncology, College of Medicine, University of Illinois at Chicago
  • , Peter ValentAffiliated withDepartment of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna
    • , Bruce S. BochnerAffiliated withDepartment of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of MedicineDivision of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center Email author 

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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.

Keywords

Siglec-8 eosinophils mast cells basophils expression hematologic malignancies cell lines