Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidaseIV reveals a striking selectivity within the chemokine family

Chemokines coordinate many aspects of leukocyte migration. As chemoattracta nts they play an important role in the innate and acquired immune response. There is good experimental evidence that N-terminal truncation by secreted or cell surface proteases is a way of modulating chemokine action. The loc alization of CD26/dipeptidyl peptidase IV on cell surfaces and in biologica l fluids, its primary specificity, and the type of naturally occurring trun cated chemokines are consistent with such a function. We determined the steady-state catalytic parameters for a relevant selectio n of chemokines (CCL3b, CCL5, CCL11, CCL22, CXCL9, CXCL10, CXCL11, and CXCL 12) previously reported to alter their chemotactic behavior due to CD26/dip eptidyl peptidase IV-catalyzed truncation. The results reveal a striking se lectivity for stromal cell-derived factor-la (CXCL12) and macrophage-derive d chemokine (CCL22). The kinetic parameters support the hypothesis that CD2 6/dipeptidyl peptidase IV contributes to the degradation of certain chemoki nes in vivo. The data not only provide insight into the selectivity of the enzyme for specific chemokines, but they also contribute to the general und erstanding of CD26/dipeptidyl peptidase IV secondary substrate specificity.