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

Nancie J. Solan, Patrick E. Ward, Scherer P. Sanders, Marilyn C. Towns, Joan M. Bathon

Research output: Contribution to journalArticlepeer-review

Abstract

Several endogenous peptides, including bradykinin and sustance 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.

Original languageEnglish (US)
Pages (from-to)107-121
Number of pages15
JournalInflammation
Volume22
Issue number1
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology
  • Cell Biology

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