Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family.
Chemokines coordinate many aspects of leukocyte migration. As chemoattractants 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 localization of CD26/dipeptidyl peptidase IV on cell surfaces and in biological fluids, its primary specificity, and the type of naturally occurring truncated chemokines are consistent with such a function. We determined the steady-state catalytic parameters for a relevant selection of chemokines (CCL3b, CCL5, CCL11, CCL22, CXCL9, CXCL10, CXCL11, and CXCL12) previously reported to alter their chemotactic behavior due to CD26/dipeptidyl peptidase IV-catalyzed truncation. The results reveal a striking selectivity for stromal cell-derived factor-1alpha (CXCL12) and macrophage-derived chemokine (CCL22). The kinetic parameters support the hypothesis that CD26/dipeptidyl peptidase IV contributes to the degradation of certain chemokines in vivo. The data not only provide insight into the selectivity of the enzyme for specific chemokines, but they also contribute to the general understanding of CD26/dipeptidyl peptidase IV secondary substrate specificity.
Lambeir
A M
AM
Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1 S6, B-2610 Antwerp, Belgium. anne-marie.lambeir@ua.ac.be
Proost
P
P
Durinx
C
C
Bal
G
G
Senten
K
K
Augustyns
K
K
Scharpé
S
S
Van Damme
J
J
De Meester
I
I
D000595:Amino Acid Sequence; D002384:Catalysis; D054412:Chemokine CCL8; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D018925:Chemokines / Q000737:chemistry / Q000378:metabolism*; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis* / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D011485:Protein Binding; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors
C515453:CCL8 protein, human; C515354:CCR4 protein, human; C515202:CXCL11 protein, human; C515255:CXCL12 protein, human; C515187:CXCR3 protein, human; D054412:Chemokine CCL8; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D018945:Monocyte Chemoattractant Proteins; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018819:Dipeptidyl Peptidase 4