Implication of dipeptidylpeptidase IV activity in human bronchial inflammation and in bronchoconstriction evaluated in anesthetized rabbits.
BACKGROUND
Decreased dipeptidylpeptidase IV (DPPIV) activity within the human nasal mucosa has previously been shown to contribute to the severity of chronic inflammatory rhinosinusitis.


OBJECTIVE
To investigate and correlate the role of DPPIV activity with regard to bronchial inflammation.


METHODS
DPPIV/CD26 activity/concentration was investigated in the bronchial tissue of human subjects suffering from chronic bronchial inflammation. In addition, the effect of a recombinant Aspergillus fumigatus DPPIV (fuDPPIV) was investigated on histamine-induced bronchoconstriction in anesthetized rabbits.


CONCLUSIONS
DPPIV/CD26 was present in submucosal seromucous glands, in leukocytes and to a very low degree in endothelial cells of human bronchi. DPPIV activity was correlated with tissue CD26 content measured by immunoassay. As previously reported for the nasal mucosa, DPPIV/CD26 activity was inversely correlated with the degree of airway inflammation. Systemic pretreatment with recombinant fuDPPIV markedly reduced the increase in histamine-induced airway resistance in rabbits. In conclusion, DPPIV activity modulates lower airway tone by degrading unknown peptidic substrates released by histamine in response to an allergen. Contrasting with our observations in the nose, this modulation is apparently not mediated via a neurokinin (NK1) receptor.
Landis
B N
BN
Rhinology-Olfactology Unit, Department of Otolaryngology, University Hospital of Geneva, Geneva, Switzerland. Basile.Landis@hcuge.ch
Grouzmann
E
E
Monod
M
M
Busso
N
N
Petak
F
F
Spiliopoulos
A
A
Robert
J H
JH
Szalay-Quinodoz
I
I
Morel
D R
DR
Lacroix
J S
JS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000201:enzymology* / Q000517:prevention & control; D029481:Bronchitis, Chronic / Q000201:enzymology* / Q000473:pathology; D016084:Bronchoconstriction / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000201:enzymology / Q000503:physiopathology; D011336:Probability; D011817:Rabbits; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013373:Substance P / Q000494:pharmacology
D015415:Biomarkers; D013373:Substance P; D006632:Histamine; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4