Struyf S, Proost P, Schols D, De Clercq E, Opdenakker G, Lenaerts J P, Detheux M, Parmentier M, De Meester I, Scharpé S, Van Damme J
Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Belgium.
J Immunol. 1999 Apr 15;162(8):4903-9.
Chemokines attract and activate distinct sets of leukocytes. The CC chemokine eotaxin has been characterized as an important mediator in allergic reactions because it selectively attracts eosinophils, Th2 lymphocytes, and basophils. Human eotaxin has a penultimate proline, indicating that it might be a substrate for dipeptidyl-peptidase IV (CD26/DPP IV). In this study we demonstrate that eotaxin is efficiently cleaved by CD26/DPP IV and that the NH2-terminal truncation affects its biological activity. CD26/DPP IV-truncated eotaxin(3-74) showed reduced chemotactic activity for eosinophils and impaired binding and signaling properties through the CC chemokine receptor 3. Moreover, eotaxin(3-74) desensitized calcium signaling and inhibited chemotaxis toward intact eotaxin. In addition, HIV-2 infection of CC chemokine receptor 3-transfected cells was inhibited to a similar extent by eotaxin and eotaxin(3-74). Thus, CD26/DPP IV differently regulates the chemotactic and antiviral potencies of eotaxin by the removal of two NH2-terminal residues. This physiological processing may be an important down-regulatory mechanism, limiting eotaxin-mediated inflammatory responses.
趋化因子可吸引并激活不同类型的白细胞。CC趋化因子嗜酸性粒细胞趋化因子已被确定为过敏反应中的一种重要介质，因为它可选择性地吸引嗜酸性粒细胞、Th2淋巴细胞和嗜碱性粒细胞。人嗜酸性粒细胞趋化因子的倒数第二个氨基酸为脯氨酸，这表明它可能是二肽基肽酶IV（CD26/DPP IV）的底物。在本研究中，我们证明嗜酸性粒细胞趋化因子可被CD26/DPP IV有效切割，且氨基末端的截短会影响其生物学活性。CD26/DPP IV截短的嗜酸性粒细胞趋化因子（3 - 74）对嗜酸性粒细胞的趋化活性降低，通过CC趋化因子受体3的结合和信号传导特性受损。此外，嗜酸性粒细胞趋化因子（3 - 74）使钙信号脱敏，并抑制对完整嗜酸性粒细胞趋化因子的趋化作用。另外，嗜酸性粒细胞趋化因子和嗜酸性粒细胞趋化因子（3 - 74）对CC趋化因子受体3转染细胞的HIV - 2感染的抑制程度相似。因此，CD26/DPP IV通过去除两个氨基末端残基，以不同方式调节嗜酸性粒细胞趋化因子的趋化和抗病毒效力。这种生理加工可能是一种重要的下调机制，可限制嗜酸性粒细胞趋化因子介导的炎症反应。
