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. Results and 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.

1.
Leynaert B, Neukirch C, Liard R, Bousquet J, Neukirch F: Quality of life in allergic rhinitis and asthma. A population-based study of young adults. Am J Respir Crit Care Med 2000;162(4 pt 1):1391–1396.
2.
Martling CR: Sensory nerves containing tachykinins and CGRP in the lower airways. Functional implications for bronchoconstriction, vasodilatation and protein extravasation. Acta Physiol Scand Suppl 1987;563:1–57.
3.
Uddman R, Sundler F: Neuropeptides in the airways: a review. Am Rev Respir Dis 1987;136(6 pt 2):S3–S8.
4.
Grouzmann E, Monod M, Landis B, Wilk S, Brakch N, Nicoucar K, et al: Loss of dipeptidylpeptidase IV activity in chronic rhinosinusitis contributes to the neurogenic inflammation induced by substance P in the nasal mucosa. FASEB J 2002;16:1132–1134.
5.
Boonacker EP, Wierenga EA, Smits HH, Van Noorden CJ: CD26/DPPIV signal transduction function, but not proteolytic activity, is directly related to its expression level on human Th1 and Th2 cell lines as detected with living cell cytochemistry. J Histochem Cytochem 2002;50:1169–1177.
6.
Busso N, Wagtmann N, Herling C, Chobaz-Peclat V, Bischof-Delaloye A, So A, et al: Circulating CD26 is negatively associated with inflammation in human and experimental arthritis. Am J Pathol 2005;166:433–442.
7.
Bousquet J, Van Cauwenberge P, Khaltaev N: Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108(5 suppl):S147–S334.
8.
Scharpé SL, Vanhoof GC, De Meester IA, Hendriks DF, van Sande ME, Muylle LM, et al: Exopeptidases in human platelets: an indication for proteolytic modulation of biologically active peptides. Clin Chim Acta 1991;195:125–131.
9.
Beauvais A, Monod M, Wyniger J, Debeaupuis JP, Grouzmann E, Brakch N, et al: Dipeptidyl-peptidase IV secreted by Aspergillus fumigatus, a fungus pathogenic to humans. Infect Immun 1997;65:3042–3047.
10.
Nausch I, Mentlein R, Heymann E: The degradation of bioactive peptides and proteins by dipeptidyl peptidase IV from human placenta. Biol Chem Hoppe Seyler 1990;371:1113–1118.
11.
Sorrell JM, Brinon L, Baber MA, Caplan AI: Cytokines and glucocorticoids differentially regulate APN/CD13 and DPPIV/CD26 enzyme activities in cultured human dermal fibroblasts. Arch Dermatol Res 2003;295:160–168.
12.
Andersson PT, Persson CG: Developments in anti-asthma glucocorticoids. Agents Actions Suppl 1988;23:239–260.
13.
Grouzmann E, Buclin T, Biollaz J: Gliptins. Lancet 2007;369:269.
14.
Nathan DM: Finding new treatments for diabetes – how many, how fast ... how good? N Engl J Med 2007;356:437–440.
15.
Lewis T: The Blood Vessels of the Human Skin and Their Responses. London, Shaw, 1927.
16.
Jancso N, Jancso-Gabor A, Szolcsanyi J: Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol Chemother 1967;31:138–151.
17.
Ollerenshaw SL, Jarvis D, Sullivan CE, Woolcock AJ: Substance P immunoreactive nerves in airways from asthmatics and nonasthmatics. Eur Respir J 1991;4:673–682.
18.
Barnes PJ, Baraniuk JN, Belvisi MG: Neuropeptides in the respiratory tract. Part II. Am Rev Respir Dis 1991;144:1391–1399.
19.
Barnes PJ, Baraniuk JN, Belvisi MG: Neuropeptides in the respiratory tract. Part I. Am Rev Respir Dis 1991;144:1187–1198.
20.
de Meester I, Lambeir AM, Proost P, Scharpe S: Dipeptidyl peptidase IV substrates. An update on in vitro peptide hydrolysis by human DPPIV. Adv Exp Med Biol 2003;524:3–17.
21.
Ohkubo K, Baraniuk JN, Hohman R, Merida M, Hersh LB, Kaliner MA: Aminopeptidase activity in human nasal mucosa. J Allergy Clin Immunol 1998;102:741–750.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.