Loss of dipeptidylpeptidase IV activity in chronic rhinosinusitis contributes to the neurogenic inflammation induced by substance P in the nasal mucosa.
In this study, we have found that dipeptidylpeptidase IV (DPPIV) plays in vivo an active role in the modulation of the inflammatory response of chronic rhinosinusitis. Human nasal mucosa expresses DPPIV-like immunoreactivity in submucosal seromucus glands, leukocytes, and endothelial cells of blood vessels. DPPIV enzymatic activity in nasal tissue biopsies taken from patients suffering from chronic rhinosinusitis was correlated inversely with the density of inflammatory cells in the nasal mucosa, and the DPPIV activity rose when chronic rhinosinusitis was treated. By using a pig animal model, we have shown that the intranasal administration of recombinant DPPIV decreased the vasodilatation induced by exogenous substance P (SP), a proinflammatory peptide released by sensory nerves. In contrast, an inhibitor of DPPIV enhanced the vasodilatatory effect at low doses of SP. SP5-11 was 100- to 1000-fold less potent than SP as a vasodilator of the nasal mucosa. The vasodilatatory effect of SP was abolished by a NK1 receptor antagonist. In conclusion, these results suggest a new pathophysiological pathway for rhinitis based on clinical observations in humans, indicating the involvement of an enzyme to modulate non-adrenergic and non-cholinergic substrate that occurred during nasal dysfunctions.
Grouzmann
Eric
E
Division d'Hypertension, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland. Eric.Grouzmann@chuv.hospvd.ch
Monod
Michel
M
Landis
Basile
B
Wilk
Sherwin
S
Brakch
Noureddine
N
Nicoucar
Kevin
K
Giger
Roland
R
Malis
Didier
D
Szalay-Quinodoz
Ildiko
I
Cavadas
Claudia
C
Morel
Denis R
DR
Lacroix
Jean-Silvain
JS
D000818:Animals; D002908:Chronic Disease; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009297:Nasal Mucosa / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology*; D012220:Rhinitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D013373:Substance P; D018819:Dipeptidyl Peptidase 4