Human nasal mucosal carboxypeptidase: activity, location, and release

Area of Science:

• Immunology
• Respiratory Medicine
• Biochemistry

Background:

• Carboxypeptidases (CPs), like carboxypeptidase N (CPN), may modulate inflammatory peptide activity in the respiratory mucosa.
• CPNs degrade inflammatory mediators such as bradykinin, impacting allergic and non-allergic inflammation.

Purpose of the Study:

• To investigate the sources of carboxypeptidase activity in human nasal secretions.
• To determine the origin of CPN in the nasal mucosa and its secretion in response to various stimuli.

Main Methods:

• Immunohistochemistry was used to identify potential CPN sources in the nasal mucosa.
• CP activity was measured in nasal lavage fluids and mucosal homogenates after provocation with saline, histamine, methacholine, and allergen.
• CP activity was quantified by Bz-Gly-Lys degradation, inhibited by DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid.

Main Results:

• CPN immunoreactivity was found in the epithelial glycocalyx, vessels, and gland ducts, but not submucosal gland cells.
• Histamine provocation significantly increased CP activity in nasal lavage fluid compared to saline (3.84 U/L vs 0.10 U/L).
• Allergen challenge led to peak CP activity correlated with IgG concentration, indicating a plasma origin.

Conclusions:

• Plasma is the primary source of CP activity secreted by the human nasal mucosa.
• Plasma extravasation and interstitial fluid exudation are key mechanisms for CP appearance in nasal secretions.