HUMAN NASAL MUCOSAL CARBOXYPEPTIDASE - ACTIVITY, LOCATION, AND RELEASE

Background: Carboxypeptidases (CPs), such as carboxypeptidase N (CPN) (kininase I, E.C.3.4.17.3), may regulate peptide-mediated vasodilation and vascular permeability in respiratory mucosa by degrading proinfla mmatory peptides such as bradykinin, anaphylatoxins, and neuropeptides during allergic and nonallergic inflammation. The sources of CP activ ity in human nasal secretions were investigated. Methods: Well-charact erized human nasal provocation and secretion analysis methods were use d. Potential sources of CPN in human nasal mucosa were identified by i mmunohistochemistry. CP activity was defined as DL-2-mercaptomethyl-3- guanidinoethylthiopropanoic acid inhibitable Bz-Gly-Lys degradation. C P activity was measured in nasal mucosal homogenates and nasal lavage fluids induced by methacholine, histamine, and allergen nasal provocat ion. Results: CPN-immunoreactive material was localized to the glycoca lyx of the epithelium, some vessels, and gland ducts near the epitheli al basement membrane but not to submucosal gland cells. CP activity in human nasal lavage fluid after saline nasal provocation was 0.10 +/- 0.04 U/L. Histamine provoked secretion of significantly more CP activi ty (3.84 +/- 0.99 U/L; p<0.01 vs saline). Methacholine did not signifi cantly increase secretion (0.54 +/- 0.22 U/L). After nasal allergen ch allenge, CP activity was at a maximum between 11 and 20 minutes, and C P activity correlated with IgG concentration (r = 0.91, p<0.01), a mar ker for proteins of plasma origin, suggesting that CP activity origina ted in plasma. Conclusions: These data suggest that plasma is the pred ominant source of CP activity secreted from human nasal mucosa and tha t plasma extravasation and interstitial fluid exudation across the epi thelium are the primary processes regulating its appearance in nasal s ecretions.