Published online before print February 7, 2007

This Article Full Text Free Full Text (PDF) Free Supplemental Data All Versions of this Article: jlb.0906546v1 81/5/1252    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maes, M.-B. Articles by De Meester, I. Search for Related Content PubMed PubMed Citation Articles by Maes, M.-B. Articles by De Meester, I.

(Journal of Leukocyte Biology. 2007;81:1252-1257.)
© 2007 by Society for Leukocyte Biology

Dipeptidyl peptidase 8/9-like activity in human leukocytes

Marie-Berthe Maes^*, Véronique Dubois^*, Inger Brandt^*, Anne-Marie Lambeir^*, Pieter Van der Veken, Koen Augustyns, Jonathan D. Cheng, Xin Chen, Simon Scharpé^* and Ingrid De Meester^*,1

Laboratories of
^* Medical Biochemistry and
Medicinal Chemistry, University of Antwerp, Wilrijk, Belgium;
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA; and
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Nankang, Taipei, Taiwan, Republic of China

¹ Correspondence: Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium. E-mail: ingrid.demeester{at}ua.ac.be

The proline-specific dipeptidyl peptidases (DPPs) are emerging as a protease family with important roles in the regulation of signaling by peptide hormones. Inhibitors of DPPs have an intriguing, therapeutic potential, with clinical efficacy seen in patients with diabetes. Until now, only recombinant forms of DPP8 and DPP9 have been characterized. Their enzymatic activities have not been demonstrated in or purified from any natural source. Using several selective DPP inhibitors, we show that DPP activity, attributable to DPP8/9 is present in human PBMC. All leukocyte types tested (lymphocytes, monocytes, Jurkat, and U937 cells) were shown to contain similar DPP8/9-specific activities, and DPPII- and DPPIV-specific activities varied considerably. The results were confirmed by DPPIV/CD26 immunocapture experiments. Subcellular fractionation localized the preponderance of DPP8/9 activity to the cytosol and DPPIV in the membrane fractions. Using Jurkat cell cytosol as a source, a 30-fold, enriched DPP preparation was obtained, which had enzymatic characteristics closely related to the ones of DPP8 and/or -9, including inhibition by allo-Ile-isoindoline and affinity for immobilized Lys-isoindoline.

Key Words: DPPIV • DPP8 • DPP9 • fibroblast activation protein • vildagliptin

This article has been cited by other articles:

				D. M.T. Yu, K. Ajami, M. G. Gall, J. Park, C. S. Lee, K. A. Evans, E. A. McLaughlin, M. R. Pitman, C. A. Abbott, G. W. McCaughan, et al. The In Vivo Expression of Dipeptidyl Peptidases 8 and 9 J. Histochem. Cytochem., November 1, 2009; 57(11): 1025 - 1040. [Abstract] [Full Text] [PDF]

				V. Dubois, C. Van Ginneken, H. De Cock, A.-M. Lambeir, P. Van der Veken, K. Augustyns, X. Chen, S. Scharpe, and I. De Meester Enzyme Activity and Immunohistochemical Localization of Dipeptidyl Peptidase 8 and 9 in Male Reproductive Tissues J. Histochem. Cytochem., June 1, 2009; 57(6): 531 - 541. [Abstract] [Full Text] [PDF]

				J. Schade, M. Stephan, A. Schmiedl, L. Wagner, A. J. Niestroj, H.-U. Demuth, N. Frerker, C. Klemann, K. A. Raber, R. Pabst, et al. Regulation of Expression and Function of Dipeptidyl Peptidase 4 (DP4), DP8/9, and DP10 in Allergic Responses of the Lung in Rats J. Histochem. Cytochem., February 1, 2008; 56(2): 147 - 155. [Abstract] [Full Text] [PDF]