Plasmin(ogen) carbohydrate chains mediate binding to dipeptidyl peptidase IV (CD 26) in rheumatoid arthritis human synovial fibroblasts

Journal Article (Journal Article)

Objective: To assess the reactivity between dipeptidyl peptidase IV (DPP IV) and the α2,3-linked sialic acid of the plasminogen (Pg)Thr345 O- linked carbohydrate chain as the mechanism enabling plasmin (Pm) to induce intracellular Ca2+ via DPP IV on rheumatoid synovial fibroblasts, and identify the DPP IV region responsible for this interaction. Methods: Cytosolic Ca2+ mobilization in rheumatoid synovial fibroblasts was assayed by Digital Imaging Microscopy (DIM). DPP IV was purified by affinity chromatography on an immobilized polysaccharide structurally analogous to the last two residues of the Pg 2 carbohydrate chain. Binding of Pg to DPP IV and identification of the DPP IV reactive site were determined by an enzyme- linked immunosorbent assay (ELISA) and inhibition of Pm-induced intracellular Ca2+ mobilization in these cells by peptides comprising three regions of DPP IV primary structure. Results: Cytosolic Ca2+ mobilization induced by Pm on rheumatoid synovial fibroblasts is inhibited by L-lactose, a sugar that interferes with sialic acid binding to lectins. Asialo Pg which binds and can be converted into Pm on the surface of these cells is not able to induce intracellular Ca2+ mobilization. A peptide comprising the DPP IV primary sequence L313QWLRRI inhibits both Pg binding to DPP IV and Pm-induced intracellular Ca2+ mobilization on these cells. Conclusion: The intracellular Ca2+ mobilization resulting from the reaction between Pg/Pm and DPP IV is mediated by a lectin-like region in DPP IV. This region is structurally analogous to the sequence (QxW)3, previously identified as a carbohydrate-binding region in several lectin families.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • January 1, 1998

Published In

Volume / Issue

  • 12 / 6

Start / End Page

  • 366 - 374

International Standard Serial Number (ISSN)

  • 1369-0191

Digital Object Identifier (DOI)

  • 10.1016/S0268-9499(98)80395-0

Citation Source

  • Scopus