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Published online before print March 22, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0604349

Received for publication June 15, 2004.
Revised February 19, 2005.
Accepted for publication February 22, 2005.

Article

Evaluation of normal and neoplastic human mast cells for expression of CD172a (SIRP), CD47, and SHP-1

Stefan Florian ^*, Minoo Ghannadan ^*, Matthias Mayerhofer ^*, Karl J. Aichberger ^*, Alexander W. Hauswirth ^*, Gerit-Holger Schernthaner ^*, Dieter Printz , Gerhard Fritsch , Alexandra Böhm ^*, Karoline Sonneck ^*, Maria-Theresa Krauth ^*, Michael R. Müller , Christian Sillaber ^*, Wolfgang R. Sperr ^*, Hans-Jörg Bühring , and Peter Valent ^*@

Departments of *Internal Medicine I, Division of Hematology & Hemostaseology, and Surgery, Medical University of Vienna, Austria; St. Anna Children’s Hospital, Vienna, Austria; and Department of Internal Medicine II, University of Tübingen, Germany

^@ To whom correspondence should be addressed. E-mail: peter.valent{at}meduniwien.ac.at.

	Abstract

Signal regulatory proteins (SIRPs) and tyrosine phosphatases have recently been implicated in the control of receptor tyrosine kinase (RTK)-dependent cell growth. In systemic mastocytosis (SM), neoplastic cells are driven by the RTK KIT, which is mutated at codon 816 in most patients. We examined expression of SIRP, SIRP ligand CD47, and Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), a tyrosine phosphatase-type, negative regulator of KIT-dependent signaling, in normal human lung mast cells (HLMC) and neoplastic MC obtained from nine patients with SM. As assessed by multicolor flow cytometry, normal LMC expressed SIRP, CD47, and SHP-1. In patients with SM, MC also reacted with antibodies against SIRP and CD47. By contrast, the levels of SHP-1 were low or undetectable in MC in most cases. Corresponding data were obtained from mRNA analysis. In fact, whereas SIRP mRNA and CD47 mRNA were detected in all samples, the levels of SHP-1 mRNA varied among donors. To demonstrate adhesive functions for SIRP and CD47 on neoplastic MC, an adhesion assay was applied using the MC leukemia cell line HMC-1, which was found to bind to immobilized extracellular domains of SIRP1 (SIRP1ex) and CD47 (CD47ex), and binding of these cells to CD47ex was inhibited by the CD172 antibody SE5A5. In summary, our data show that MC express functional SIRP and CD47 in SM, whereas expression of SHP-1 varies among donors and is low compared with LMC. It is hypothesized that CD172 and CD47 contribute to MC clustering and that the "lack" of SHP-1 in MC may facilitate KIT-dependent signaling in a subgroup of patients.

Key Words: mastocytosis • SCF • c-kit • signal transduction

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