K. Ohkubo et al., HUMAN NASAL MUCOSAL CARBOXYPEPTIDASE - ACTIVITY, LOCATION, AND RELEASE, Journal of allergy and clinical immunology, 96(6), 1995, pp. 924-931
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.