Amino-terminal processing of MIP-1beta/CCL4 by CD26/dipeptidyl-peptidase IV

CD26 is a membrane-bound ectopeptidase with dipeptidyl peptidase IV (DPPIV) activity that has diverse functional properties in T cell physiology and in regulation of bioactive peptides. We have previously reported that activated human peripheral lymphocytes (PBL) secrete an amino-terminal truncated form of macrophage inflammatory protein (MIP)-1beta/(3-69) with novel functional specificity for CCR1, 2, and 5. In this report, we show that the full length MIP-1beta is processed by CD26/DPPIV to the truncated form and that cleavage can be blocked by DPPIV inhibitory peptides derived from HIV Tat(1-9) or the thromboxane A2 receptor, TAX2-R(1-9). Addition of Tat(1-9) or TAX2-R(1-9) peptides to PBL cultures partially blocks endogenous MIP-1beta processing. The kinetics of conversion of MIP-1beta from intact to MIP-1beta(3-69) in activated PBLs correlates with cell surface expression of CD26. Our results suggest that NH2-terminal processing of MIP-1beta and possibly other chemokines may depend on the balance between CD26/DPPIV enzymatic activity and cellular and viral proteins that modulate enzyme function.