Plasmin(ogen) carbohydrate chains mediate binding to dipeptidyl peptidase iv (cd 26) on rheumatoid artrhitis human synovial fibroblasts

Published

Journal Article

Both plasminogen (Pg) and the streptococcal plasminogen activator streptokinase (SK) bind to synovial fibroblasts from patients with rheumatoid arthritis (RA) with a very high affinity and in a dose-dependent manner. The receptor for both proteins has been identified as dipeptidyl peptidase IV (DPP IV). Pg can be activated by SK on the surface of RA synovial fibroblasts inducing an enhanced cytosolic calcium mobilization comparable to the response observed after Pg activation by urinary-type plasminogen activator (uPA). Intracellular calcium mobilization can also be induced by Pg in the open conformation, suggesting that conversion to plasmin (Pm) is not necessary for signal transduction. The rise in intracellular calcium concentration produced by Pg or Pm can be inhibited by l-lactose suggesting a mechanism which involves a lectin-like interaction of DPP IV with these ligands. We were able to purify DPP IV by affinity chromatography with an immobilized disaccharide structurally analogous to the last two residues of the Pg 2 carbohydrate chain, thereby confirming the lectin properties of DPP IV. There are six Pg 2 glycoforms containing only one carbohydrate chain attached to Thr345 which differ in their α2,3-sialic acid contents. Studies with isolated glycoforms were also performed. Our results suggest that the length of the polysialic acid chain is a determinant factor of the ability of these Pg glycoforms to induce signal transduction.

Full Text

Duke Authors

Cited Authors

  • Gonzalez-Gronow, M; Gawdi, G; Shearin, TV; Pirie-Shepherd, SR; Pizzo, SV

Published Date

  • January 1, 1996

Published In

Volume / Issue

  • 10 / SUPPL. 3

Start / End Page

  • 25 -

International Standard Serial Number (ISSN)

  • 0268-9499

Digital Object Identifier (DOI)

  • 10.1016/s0268-9499(96)80163-9

Citation Source

  • Scopus