Up-regulation of the alpha2-macroglobulin signaling receptor on rheumatoid synovial fibroblasts.

Journal Article (Journal Article)

In the present study, we demonstrate that the alpha2-macroglobulin (alpha2M) signaling receptor is up-regulated on rheumatoid synovial fibroblasts. In rheumatoid cells, 125I-alpha2M-methylamine bound to two sites; namely, one of high affinity (Kd approximately 52 pM) and the second of lower affinity (Kd approximately 9.7 nM). In normal synovial fibroblasts only one site for 125I-alpha2M-methylamine (Kd approximately 5.36 nM) was present. Receptor-associated protein did not inhibit the binding of alpha2M-methylamine to the high affinity binding sites, but it caused a 70-80% reduction in its binding to low affinity binding sites establishing its identity as the low density lipoprotein receptor-related protein/alpha2M receptor. Binding of alpha2M-methylamine to rheumatoid but not normal synovial fibroblasts caused a rapid rise in inositol 1,4,5-trisphosphate synthesis with a peak reached within 10 s of ligand exposure. Concomitantly, rheumatoid but not normal cells showed a rise in intracellular Ca2+. Pretreatment of rheumatoid cells with Receptor-associated protein or pertussis toxin did not affect the alpha2M-methylamine-induced increase in intracellular Ca2+. These are characteristic properties of ligation by alpha2M-methylamine of the alpha2M signaling receptor but not the lipoprotein receptor-related protein/alpha2M receptor. Binding of alpha2M-methylamine to rheumatoid synovial fibroblasts significantly increased the synthesis of DNA compared with normal synovial fibroblasts treated similarly.

Full Text

Duke Authors

Cited Authors

  • Misra, UK; Gonzalez-Gronow, M; Gawdi, G; Pizzo, SV

Published Date

  • January 3, 1997

Published In

Volume / Issue

  • 272 / 1

Start / End Page

  • 497 - 502

PubMed ID

  • 8995289

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.272.1.497


  • eng

Conference Location

  • United States