Peptidase activities in serum and bronchoalveolar lavage fluid from allergic asthmatics--comparison with healthy non-smokers and smokers and effects of inhaled glucocorticoids.
BACKGROUND
Neuropeptides may be involved in the pathogenesis of asthma by evoking neurogenic inflammation. Since the effects of neuropeptides are limited by peptidases, reduced activity of peptidases may contribute to the inflammatory process.


OBJECTIVE
We hypothesized that soluble peptidase activities are decreased in asthmatics and that inhaled glucocorticoids exert part of their anti-inflammatory action by increasing soluble peptidase activities.


METHODS
Serum and bronchoalveolar lavage (BAL) fluid was obtained from non-smoking and smoking volunteers and from allergic asthmatics both before and after treatment for 12 weeks with placebo or inhaled fluticasone propionate. Activities of neutral endopeptidase (NEP), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV) were determined using colourometric assays.


RESULTS
Reduced DPP IV activity in serum and reduced NEP activity in BAL fluid were found in healthy smokers compared with non-smokers. In contrast, no differences in peptidase activities in serum or BAL fluid were observed between allergic asthmatics and healthy non-smokers. Fluticasone propionate treatment did not affect peptidase activities in the asthmatic patients.


CONCLUSIONS
We conclude that reduced peptidase activities in serum or BAL fluid can be found in healthy smokers, but not in allergic asthmatics, and that inhaled glucocorticoids do not affect peptidase activities in BAL fluid or serum of asthmatics. Our results do not support the hypothesized dysfunction of peptidases in the asthmatic airways.
Van Der Velden
V H
VH
Immunology; Pulmonary Medicine, Erasmus University and University Hospital Dijkzigt, Rotterdam, The Netherlands.
Naber
B A
BA
Van Hal
P T
PT
Overbeek
S E
SE
Hoogsteden
H C
HC
Versnel
M A
MA
D000280:Administration, Inhalation; D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D018826:CD13 Antigens / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D012016:Reference Values; D012907:Smoking
D000730:Androstadienes; D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D000068298:Fluticasone; D018826:CD13 Antigens; D018819:Dipeptidyl Peptidase 4; D015260:Neprilysin