PMID- 10572074
OWN - NLM
STAT- MEDLINE
DCOM- 19991230
LR  - 20171116
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 11
DP  - 1999 Dec 1
TI  - Human signal-regulatory protein is expressed on normal, but not on subsets of
      leukemic myeloid cells and mediates cellular adhesion involving its
      counterreceptor CD47.
PG  - 3633-43
AB  - Signal-regulatory proteins (SIRPs) comprise a novel transmembrane glycoprotein
      family involved in the negative regulation of receptor tyrosine kinase-coupled
      signaling pathways. To analyze the expression and function of SIRPs, we prepared 
      soluble recombinant fusion proteins of the extracellular regions of SIRPalpha1
      and SIRPalpha2, as well as a variety of monoclonal antibodies (MoAbs) against
      these domains. The antibodies reacted predominantly with monocytes, granulocytes,
      dendritic cells, and their precursors, as well as with bone marrow CD34(+),
      AC133(+), CD90(+) hematopoietic stem/progenitor cells. In contrast, SIRP
      expression was absent or significantly reduced on the majority of myeloid blasts 
      from patients with acute myeloid leukemia (AML) or chronic myeloid leukemia
      (CML). Functional studies showed that the extracellular domains of SIRPalpha1 and
      SIRPalpha2 support adhesion of a number of primary hematopoietic cells and cell
      lines. This interaction could be blocked by 4 of 7 SIRPalpha1-reactive MoAbs. In 
      addition, SIRPalpha1 and SIRPalpha2 competed for the same cell binding site,
      suggesting a common widely expressed SIRP ligand. In an approach to identify this
      molecule, MoAbs were generated against the SIRP-binding cell line CCRF-CEM, and
      MoAb CC2C6 was selected because of its capacity to inhibit cell binding to
      SIRPalpha1. Further analysis showed that this antibody recognized CD47, a
      ubiquitously expressed plasma membrane protein previously implicated in integrin 
      function, host defense action, and neutrophil migration. In this study, we
      identify CD47 as the extracellular ligand for human SIRP and show that these two 
      counterreceptors are involved in cellular adhesion.
FAU - Seiffert, M
AU  - Seiffert M
AD  - University of Tubingen, the Department of Internal Medicine II, Tubingen,
      Germany.
FAU - Cant, C
AU  - Cant C
FAU - Chen, Z
AU  - Chen Z
FAU - Rappold, I
AU  - Rappold I
FAU - Brugger, W
AU  - Brugger W
FAU - Kanz, L
AU  - Kanz L
FAU - Brown, E J
AU  - Brown EJ
FAU - Ullrich, A
AU  - Ullrich A
FAU - Buhring, H J
AU  - Buhring HJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CD47 Antigen)
RN  - 0 (CD47 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neural Cell Adhesion Molecule L1)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (SIRPA protein, human)
SB  - AIM
SB  - IM
MH  - Antigens, CD/*biosynthesis
MH  - *Antigens, Differentiation
MH  - Bone Marrow Cells/*metabolism/pathology
MH  - CD47 Antigen
MH  - Carrier Proteins/*biosynthesis
MH  - Cell Adhesion
MH  - Cells, Cultured
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*metabolism/pathology
MH  - Membrane Glycoproteins/*biosynthesis
MH  - *Neural Cell Adhesion Molecule L1
MH  - Neural Cell Adhesion Molecules/*biosynthesis
MH  - *Receptors, Immunologic
MH  - Signal Transduction
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Dec 1;94(11):3633-43.