Inflammation

, Volume 22, Issue 1, pp 107–121

Soluble Recombinant Neutral Endopeptidase (CD10) as a Potential Antiinflammatory Agent

Authors

  • Nancie J. Solan
    • Department of MedicineThe Johns Hopkins University School of Medicine
  • Patrick E. Ward
    • Department of PhysiologyThe Ohio State University
  • Scherer P. Sanders
    • Department of MedicineThe Johns Hopkins University School of Medicine
  • Marilyn C. Towns
    • Department of MedicineThe Johns Hopkins University School of Medicine
  • Joan M. Bathon
    • Department of MedicineThe Johns Hopkins University School of Medicine
Article

DOI: 10.1023/A:1022304025789

Cite this article as:
Solan, N.J., Ward, P.E., Sanders, S.P. et al. Inflammation (1998) 22: 107. doi:10.1023/A:1022304025789

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.

Copyright information

© Plenum Publishing Corporation 1998