Angiotensin-converting enzyme in the human nasal mucosa.
Angiotensin-converting enzyme (ACE; EC 3.4.15.1) may participate in respiratory inflammatory diseases by regulating levels of inflammatory peptides such as bradykinin. The presence of ACE in the human nasal mucosa and in nasal secretions was determined by immunohistochemistry, measures of enzyme activity, and immunoblot. ACE activity was significantly more abundant in the membrane-rich fraction than in the soluble cytosolic fraction of nasal mucosal extracts (74.18 +/- 24.50 versus 3.99 +/- 1.83 pmol/min/mg protein, respectively, P < 0.01 by an enkephalin degradation assay; 89.16 +/- 16.17 versus 2.30 +/- 0.89 mU/mg protein, P < 0.01 by colorimetric assessment of Bz-Gly-Gly-Gly degradation). Topical application of histamine stimulated secretion of ACE activity into nasal lavage fluid (2.90 +/- 0.88 versus 1.53 +/- 0.45 U/liter after saline provocation, P < 0.05 by Bz-Gly-Gly-Gly assay). Allergen challenge also induced nasal secretion of ACE. In both histamine and allergen challenges, ACE release correlated closely with that of the vascular proteins IgG and albumin. Methacholine, a stimulant of glandular secretions, failed to augment ACE levels above baseline. ACE-immunoreactive material was localized by the immunogold technique with silver enhancement to the glycocalyx, between epithelial cells, and to interstitial, extracellular sites in the superficial lamina propria, with the highest intensity of staining immediately beneath the basement membrane. Some ACE was detectable in the mucus material of gland and duct lumens but not in gland cells themselves. Endothelial cells and some interstitial mononuclear cells also stained for ACE. ACE was identified by immunoblotting as a 150 kD band on SDS-PAGE.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohkubo
K
K
Allergic Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Lee
C H
CH
Baraniuk
J N
JN
Merida
M
M
Hausfeld
J N
JN
Kaliner
M A
MA
D000328:Adult; D000485:Allergens / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002458:Cell Fractionation; D002462:Cell Membrane / Q000201:enzymology; D003124:Colorimetry; D003600:Cytosol / Q000201:enzymology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D007700:Kinetics; D007781:Lactoferrin / Q000032:analysis; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000378:metabolism*; D011506:Proteins / Q000032:analysis; D007507:Therapeutic Irrigation
D000485:Allergens; D007074:Immunoglobulin G; D011506:Proteins; D001285:Atropine; D006632:Histamine; D007703:Peptidyl-Dipeptidase A; D007781:Lactoferrin