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

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 investiga- tion for the treatment of Type 2 diabetes, rheuma- toid 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(NO 2 ))-thiazolidide. DP IV immuno- reactivity was not detectable on monocytes, and DP IV transcript levels of monocytes were near the detection limit of quantitative polymerase chain reaction. It is interesting that monocytes exhibit a strong mRNA expression of the multifunctional DP IV-like ectoenzyme attractin and were highly pos- itive for attractin in flow cytometric analysis. Flu- orescence microscopy clearly demonstrated that attractin is located on the cell surface of mono- cytes. Attractin immunoprecipitates hydrolyzed Gly-Pro-pNA, indicating that monocyte-expressed attractin possesses DP IV-like activity. Inhibitor kinetic studies with purified human plasma attrac- tin revealed that Lys(Z(NO 2 ))-thiazolidide not only inhibits DP IV but also attractin (50% inhibition concentration8.4510 9 M). Studying the influ- ence of this inhibitor on monocyte functions, we observed a clear reduction of cell adhesion to fi- bronectin-coated culture plates in the presence of Lys(Z(NO 2 ))-thiazolidide. Moreover, this inhibitor significantly modulates the production of interleu- kin-1 (IL-1) receptor antagonist, IL-6, and trans- forming growth factor-1 in lipopolysaccharide-stim- ulated 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. J. Leukoc. Biol. 80: 000-000; 2006.