CD47, a ligand for the macrophage fusion receptor, participates in macrophage multinucleation.
The macrophage fusion receptor (MFR), also called P84/BIT/SIRPalpha/SHPS-1, is a transmembrane glycoprotein that belongs to the superfamily of immunoglobulins. Previously, we showed that MFR expression is highly induced at the onset of fusion in macrophages, and that MFR appears to play a role in macrophage-macrophage adhesion/fusion leading to multinucleation. The recent finding that IAP/CD47 acts as a ligand for MFR led us to hypothesize that it interacts with CD47 at the onset of cell-cell fusion. CD47 is a transmembrane glycoprotein, which, like MFR, belongs to the superfamily of immunoglobulins. We show that macrophages express the hemopoietic form of CD47, the expression of which is induced at the onset of fusion, but to a lower level than MFR. A glutathione S-transferase CD47 fusion protein engineered to contain the extracellular domain of CD47, binds macrophages, associates with MFR, and prevents multinucleation. CD47 and MFR associate via their amino-terminal immunoglobulin variable domain. Of the nine monoclonal antibodies raised against the extracellular domain of CD47, three block fusion, as well as MFR-CD47 interaction, whereas the others have no effect. Together, these data suggest that CD47 is involved in macrophage multinucleation by virtue of interacting with MFR during adhesion/fusion.
Han
X
X
Yale University School of Medicine, Departments of Cell Biology and Orthopaedics and Rehabilitation, New Haven, Connecticut 06510, USA.
Sterling
H
H
Chen
Y
Y
Saginario
C
C
Brown
E J
EJ
Frazier
W A
WA
Lindberg
F P
FP
Vignery
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000943:Antigens, Differentiation; D001483:Base Sequence; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D002459:Cell Fusion; D002467:Cell Nucleus / Q000648:ultrastructure*; D017931:DNA Primers; D008024:Ligands; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000648:ultrastructure; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D011971:Receptors, Immunologic
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D051928:CD47 Antigen; D002352:Carrier Proteins; D017931:DNA Primers; D008024:Ligands; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D011971:Receptors, Immunologic