The intracellular domain of CD44 promotes the fusion of macrophages. Blood 2006 Jan 15;107(2):796-805
Date
10/01/2005Pubmed ID
16195325Pubmed Central ID
PMC1473173DOI
10.1182/blood-2005-05-1902Scopus ID
2-s2.0-30444441681 (requires institutional sign-in at Scopus site) 95 CitationsAbstract
Macrophages seed all tissues in which they have the ability, in specific and rare instances, to fuse with themselves and to differentiate into osteoclasts in bone or into giant cells in chronic inflammatory reactions. Although these cells play a central role in osteoporosis and in foreign body rejection, respectively, the molecular mechanism used by macrophages to fuse remains poorly understood. Macrophages might also fuse with somatic and tumor cells to promote tissue repair and metastasis, respectively. We reported that CD44 expression is highly induced in macrophages at the onset of fusion in which it plays a role. We report now that the intracellular domain of CD44 (CD44ICD) is cleaved in macrophages undergoing fusion and that presenilin inhibitors prevent the release of CD44ICD and fusion. We also show that CD44ICD promotes the fusion of tissue macrophages and bone marrow-derived macrophages. Finally, we report that CD44ICD is localized in the nucleus of macrophages in which it promotes the activation of NF-kappaB. These observations open avenues to study the role of CD44ICD in blood cells and tumors.
Author List
Cui W, Ke JZ, Zhang Q, Ke HZ, Chalouni C, Vignery AMESH terms used to index this publication - Major topics in bold
AnimalsBone Marrow
Carrier Proteins
Cell Fusion
Cell Nucleus
Electrophoretic Mobility Shift Assay
Hyaluronan Receptors
Luciferases
Macrophages, Alveolar
Macrophages, Peritoneal
Membrane Glycoproteins
Membrane Proteins
Mice
NF-kappa B
Presenilin-1
Protein Structure, Tertiary
RANK Ligand
Rats
Rats, Inbred F344
Receptor Activator of Nuclear Factor-kappa B
Retroviridae
Subcellular Fractions
