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

Jutta Schade ¹, Michael Stephan ¹, Andreas Schmiedl ¹, Leona Wagner ¹, André J. Niestroj ¹, Hans-Ulrich Demuth ¹, Nadine Frerker ¹, Christian Klemann ¹, Kerstin A. Raber ¹, Reinhard Pabst ¹ and Stephan von Hörsten ^1*

¹ 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)

^* To whom correspondence should be addressed. E-mail: Stephan.v.Hoersten{at}ze.uni-erlangen.de.

Submitted on July 18, 2007
Accepted on 10 October 2007

	Abstract

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 dipeptidyl peptidase 10 (DP10) represents a susceptibility locus for asthma in humans and the functional homologues dipeptidyl peptidases 8 and 9 (DP8/9) are expressed in human leukocytes. Thus, while 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 that not only the induction of experimental asthma increases DP4 enzymatic activity in the bronchoalveolar lavage (BAL) 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.

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

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