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Related Collections Phagocytes Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2000, Vol. 96, No. 5, pp. 1674-1680 Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78 into a most efficient monocyte attractant and CCR1 agonist Paul Proost, Patricia Menten, Sofie Struyf, Evemie Schutyser, Ingrid De Meester, and Jo Van Damme From the Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium, and the Department of Clinical Biochemistry, University of Antwerp, Wilrijk, Belgium. Chemokines are proinflammatory cytokines that play a role in leukocyte migration and activation. Recent reports showed that RANTES (regulated on activation normal T-cell expressed and secreted chemokine), eotaxin, macrophage-derived chemokine (MDC), and stromal cell-derived factor-1 (SDF-1) are NH2-terminally truncated by the lymphocyte surface glycoprotein and protease CD26/dipeptidyl peptidase IV (CD26/DPP IV). Removal of the NH2-terminal dipeptide resulted in impaired inflammatory properties of RANTES, eotaxin, MDC, and SDF-1. The potential CD26/DPP IV substrate macrophage inflammatory protein-1 (MIP-1) and the related chemokine, LD78 (ie, one of the MIP-1 isoforms), were not affected by this protease. However, CD26/DPP IV cleaved LD78, a most potent CCR5 binding chemokine and inhibitor of macrophage tropic human immunodeficiency virus-1 (HIV-1) infection, into LD78(3-70). Naturally truncated LD78(3-70), but not truncated MIP-1, was recovered as an abundant chemokine form from peripheral blood mononuclear cells. In contrast to all other chemokines processed by CD26/DPP IV, LD78(3-70) had increased chemotactic activity in comparison to intact LD78. With a minimal effective concentration of 30 pmol/L, LD78(3-70) became the most efficient monocyte chemoattractant. LD78(3-70) retained its high capacity to induce an intracellular calcium increase in CCR5-transfected cells. Moreover, on CCR1 transfectants, truncated LD78(3-70) was 30-fold more potent than intact LD78. Thus, CD26/DPP IV can exert not only a negative but also a positive feedback during inflammation by increasing the specific activity of LD78. CD26/DPP IV-cleaved LD78(3-70) is the most potent CCR1 and CCR5 agonist that retains strong anti-HIV-1 activity, indicating the importance of the chemokine-protease interaction in normal and pathologic conditions. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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