Soluble recombinant neutral endopeptidase (CD10) as a potential antiinflammatory agent.

Journal Article

Several endogenous peptides, including bradykinin and substance P, have potent inflammatory effects in the joint. Levels of these peptides are regulated by plasma and cell-associated peptide degrading enzymes. One of these peptidases, neutral endopeptidase-24.11 (NEP-24.11), is expressed constitutively and in high density on human synovial cells and is presumed to play a critical role in local regulation of peptide levels in the joint. We examined the role of endogenous NEP-24.11 in regulating bradykinin-mediated effects in an articular model, and investigated the ability of soluble, recombinant human NEP-24.11 to augment the effects of the endogenous enzyme. Our studies demonstrate that endogenous synovial NEP-24.11 does not significantly modulate inflammatory peptide effects on cells when competing with colocalizing peptide receptors expressed in high density. Administration of excess, soluble recombinant NEP-24.11 can overcome this problem, however. Furthermore, the activity of the recombinant enzyme was not compromised in the presence of oxidants or inflammatory joint fluids. Recombinant NEP-24.11 holds promise as a novel therapeutic strategy for the treatment of inflammatory arthritis.

Full Text

Duke Authors

Cited Authors

  • Solan, NJ; Ward, PE; Sanders, SP; Towns, MC; Bathon, JM

Published Date

  • February 1998

Published In

Volume / Issue

  • 22 / 1

Start / End Page

  • 107 - 121

PubMed ID

  • 9484654

International Standard Serial Number (ISSN)

  • 0360-3997

Language

  • eng

Conference Location

  • United States