Amino-terminal processing of MIP-1β/CCL4 by CD26/dipeptidyl-peptidase IV
Amino-terminal processing of MIP-1β/CCL4 by CD26/dipeptidyl-peptidase IV
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DOI：
10.1002/jcb.20041
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发表时间：
2004-05-01
影响因子：
4
通讯作者：
Norcross, MA
中科院分区：
文献类型：
--
作者：
Guan, EN;Wang, J;Norcross, MA
CD 26是具有二肽基肽酶IV（DPPIV）活性的膜结合外肽酶，其在T细胞生理学和生物活性肽的调节中具有多种功能特性。我们以前曾报道，活化的人外周淋巴细胞（PBL）分泌一种氨基末端截短形式的巨噬细胞炎性蛋白（MIP）-1 β/（3-69），对CCR 1、2和5具有新的功能特异性。在本报告中，我们表明全长MIP-1 β被CD 26/DPPIV加工成截短形式，并且切割可以被来自HIV达特（1-9）或血栓烷A2受体TAX 2-R（1-9）的DPPIV抑制肽阻断。向PBL培养物中添加达特（1 - 9）或TAX 2-R（1 - 9）肽部分阻断内源性MIP-1 β加工。活化的PBL中MIP-1 β从完整转化为MIP-1 β（3-69）的动力学与CD 26的细胞表面表达相关。我们的研究结果表明，MIP-1 β和可能的其他趋化因子的NH 2-末端加工可能取决于CD 26/DPPIV酶活性和细胞和病毒蛋白质之间的平衡，调节酶的功能。(C)2004威利-利斯公司
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)-1 beta/(3-69) with novel functional specificity for CCR1, 2, and 5. In this report, we show that the full length MIP-1 beta 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(] -9) or TAX2-R(l -9) peptides to PBL cultures partially blocks endogenous MIP-1 beta processing. The kinetics of conversion of MIP-1 beta from intact to MIP-1 beta(3-69) in activated PBLs correlates with cell surface expression of CD26. Our results suggest that NH2-terminal processing of MIP-1 beta and possibly other chemokines may depend on the balance between CD26/DPPIV enzymatic activity and cellular and viral proteins that modulate enzyme function. (C) 2004 Wiley-Liss, Inc.