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 proinflammatory peptides such as bradykinin, anaphylatoxins, and neuropeptides during allergic and nonallergic inflammation. The sources of CP activity in human nasal secretions were investigated.


METHODS
Well-characterized human nasal provocation and secretion analysis methods were used. Potential sources of CPN in human nasal mucosa were identified by immunohistochemistry. CP activity was defined as DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid inhibitable Bz-Gly-Lys degradation. CP activity was measured in nasal mucosal homogenates and nasal lavage fluids induced by methacholine, histamine, and allergen nasal provocation.


RESULTS
CPN-immunoreactive material was localized to the glycocalyx of the epithelium, some vessels, and gland ducts near the epithelial 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 activity (3.84 +/- 0.99 U/L; p < 0.01 vs saline). Methacholine did not significantly increase secretion (0.54 +/- 0.22 U/L). After nasal allergen challenge, CP activity was at a maximum between 11 and 20 minutes, and CP activity correlated with IgG concentration (r = 0.91, p < 0.01), a marker for proteins of plasma origin, suggesting that CP activity originated in plasma.


CONCLUSIONS
These data suggest that plasma is the predominant source of CP activity secreted from human nasal mucosa and that plasma extravasation and interstitial fluid exudation across the epithelium are the primary processes regulating its appearance in nasal secretions.
Department of Otolaryngology, Nippon Medical School, Tokyo, Japan.
K
K
Ohkubo
J N
JN
Baraniuk
M
M
Merida
J N
JN
Hausfeld
H
H
Okada
M A
MA
Kaliner
D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D001826:Body Fluids / Q000201:enzymology; D002268:Carboxypeptidases / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000201:enzymology*; D009299:Nasal Provocation Tests; D007507:Therapeutic Irrigation
D000485:Allergens; D016210:Methacholine Chloride; D006632:Histamine; D002268:Carboxypeptidases