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Regulation of Expression and Function of Dipeptidyl Peptidase 4 (DP4), DP8/9, and DP10 in Allergic Responses of the Lung in Rats

Jutta Schade, Michael Stephan, Andreas Schmiedl, Leona Wagner, André J. Niestroj, Hans-Ulrich Demuth, Nadine Frerker, Christian Klemann, Kerstin A. Raber, Reinhard Pabst and Stephan von Hörsten

Department of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany (JS,MS,AS,NF,CK,RP,SvH); Probiodrug AG, Halle (Saale), Germany (LW,AJN,H-UD); and Experimental Therapy, Franz Penzoldt Center, University of Erlangen, Erlangen, Germany (KAR,SvH)

Correspondence to: Dr. Stephan von Hörsten, Experimental Therapy, Franz Penzoldt Center, Friedrich-Alexander University, Erlangen-Nürnberg, Palmsanlage 5, 91054 Erlangen, Germany. E-mail: Stephan.v.Hoersten{at}ze.uni-erlangen.de

The expression of dipeptidyl peptidase 4 (DP4, CD26) affects T-cell recruitment to lungs in an experimental rat asthma model. Furthermore, the gene of the structural homologous DP10 represents a susceptibility locus for asthma in humans, and the functional homologous DP8/9 are expressed in human leukocytes. Thus, although several mechanisms may account for a role of DP4-like peptidases in asthma, detailed information on their anatomical sites of expression and function in lungs is lacking. Therefore, bronchi and lung parenchyma were evaluated using immunohistochemistry and histochemical/enzymatic activity assays, as well as quantitative real-time PCR for this family of peptidases in naïve and asthmatic rat lungs derived from wild-type F344 and DP4-deficient F344 rat strains. Surprisingly, results show not only that the induction of experimental asthma increases DP4 enzymatic activity in the bronchoalveolar lavage fluid and parenchyma, but also that DP8/9 enzymatic activity is regulated and, as well as the expression of DP10, primarily found in the bronchial epithelium of the airways. This is the first report showing a differential and site-specific DP4-like expression and function in the lungs, suggesting a pathophysiologically significant role in asthma. (J Histochem Cytochem 56:147–155, 2008)

Key Words: dipeptidyl peptidase 4 • dipeptidyl peptidases 8/9 • dipeptidyl peptidase 10 • asthma • lung • bronchi • F344 rat substrains • DP4-like activity

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