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Originally published online as doi:10.1189/jlb.1105678 on July 11, 2006

Published online before print July 11, 2006
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(Journal of Leukocyte Biology. 2006;80:621-629.)
© 2006 by Society for Leukocyte Biology

Attractin, a dipeptidyl peptidase IV/CD26-like enzyme, is expressed on human peripheral blood monocytes and potentially influences monocyte function

Sabine Wrenger*,1, Jürgen Faust{dagger}, Daniel Friedrich{ddagger}, Torsten Hoffmann{ddagger}, Roland Hartig*, Uwe Lendeckel§, Thilo Kähne§, Anja Thielitz, Klaus Neubert{dagger} and Dirk Reinhold*

* Institutes of Immunology and
§ Experimental Internal Medicine and
Department of Dermatology and Venereology, Otto-von-Guericke-University Magdeburg, Germany;
{dagger} Institute of Biochemistry, Department of Biochemistry and Biotechnology, Martin-Luther University of Halle-Wittenberg, Halle, Germany; and
{ddagger} Probiodrug, Halle, Germany

1 Correspondence: Institute of Immunology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. E-mail: sabine.wrenger{at}medizin.uni-magdeburg.de

The ectoenzyme dipeptidyl peptidase IV (DP IV; CD26) was shown to play a crucial role in T cell activation. Several compounds inhibiting DP IV-like activity are currently under investigation for the treatment of Type 2 diabetes, rheumatoid arthritis, colitis ulcerosa, psoriasis, multiple sclerosis, and other diseases. In the present study, we show that human peripheral blood monocytes express a DP IV-like enzyme activity, which could be inhibited completely by the synthetic DP IV inhibitor Lys[Z(NO2)]-thiazolidide. DP IV immunoreactivity was not detectable on monocytes, and DP IV transcript levels of monocytes were near the detection limit of quantitative polymerase chain reaction. However, monocytes exhibit a strong mRNA expression of the multifunctional DP IV-like ectoenzyme attractin and were highly positive for attractin in flow cytometric analysis. Fluorescence microscopy clearly demonstrated that attractin is located on the cell surface of monocytes. Attractin immunoprecipitates hydrolyzed Gly-Pro-pNA, indicating that monocyte-expressed attractin possesses DP IV-like activity. Inhibitor kinetic studies with purified human plasma attractin revealed that Lys[Z(NO2)]-thiazolidide not only inhibits DP IV but also attractin (50% inhibition concentration=8.45x10–9 M). Studying the influence of this inhibitor on monocyte functions, we observed a clear reduction of cell adhesion to fibronectin-coated culture plates in the presence of Lys[Z(NO2)]-thiazolidide. Moreover, this inhibitor significantly modulates the production of interleukin-1 (IL-1) receptor antagonist, IL-6, and transforming growth factor-ß1 in lipopolysaccharide-stimulated monocyte cultures. In summary, here, we demonstrate for the first time expression of attractin on monocytes and provide first data suggesting that drugs directed to DP IV-like enzyme activity could affect monocyte function via attractin inhibition.

Key Words: DP IV inhibitor • counter-current elutriation • cytokine production • cell adhesion