Evaluation of normal and neoplastic human mast cells for expression of CD172a (SIRPalpha), CD47, and SHP-1.
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 SIRPalpha, SIRPalpha 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 SIRPalpha, CD47, and SHP-1. In patients with SM, MC also reacted with antibodies against SIRPalpha 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 SIRPalpha mRNA and CD47 mRNA were detected in all samples, the levels of SHP-1 mRNA varied among donors. To demonstrate adhesive functions for SIRPalpha 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 SIRPalpha1 (SIRPalpha1ex) 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 SIRPalpha 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.
Florian
Stefan
S
Department of Internal Medicine, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria.
Ghannadan
Minoo
M
Mayerhofer
Matthias
M
Aichberger
Karl J
KJ
Hauswirth
Alexander W
AW
Schernthaner
Gerit-Holger
GH
Printz
Dieter
D
Fritsch
Gerhard
G
Böhm
Alexandra
A
Sonneck
Karoline
K
Krauth
Maria-Theresa
MT
Müller
Michael R
MR
Sillaber
Christian
C
Sperr
Wolfgang R
WR
Bühring
Hans-Jörg
HJ
Valent
Peter
P
D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000943:Antigens, Differentiation; D000970:Antineoplastic Agents / Q000494:pharmacology; D051928:CD47 Antigen; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D034721:Mastocytosis, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011971:Receptors, Immunologic
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D051928:CD47 Antigen; C497894:CD47 protein, human; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C501920:SIRPA protein, human; D054645:Protein Phosphatase 1; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases