Shi Guo-Ping
Harvard Medical School, Cardiovascular Medicine, Brigham and Women's Hospital, NRB-7, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Future Cardiol. 2007 Nov;3(6):591-3. doi: 10.2217/14796678.3.6.591.
Evaluation of: Pagano MB, Bartoli MA, Ennis TL et al.: Critical role of dipeptidyl peptidase I in neutrophil recruitment during the development of experimental abdominal aortic aneurysms. Proc. Natl Acad. Sci. USA 104(8), 2855-2860 (2007). In this study, the authors used dipeptidyl peptidase I (DPPI) gene-targeted mice and an aortic elastase perfusion-induced mouse abdominal aortic aneurysm (AAA) model to examine the role of DPPI, also termed cathepsin C, in the development of AAA. Mice lacking this protease are resistant to AAA formation. Interestingly, these authors found that DPPI activity controls neutrophil recruitment to the sites of inflammation, specifically AAA lesions in this case. By producing chemokine CXCL2, neutrophils in AAA lesions recruit additional neutrophils to the lesion sites where these cells utilize DPPI to activate neutrophil serine proteases, including neutrophil elastase, cathepsin G and proteinase 3, which may be further used to stimulate macrophage cytokine and chemokine production. In addition to DPPI-deficient mice, the authors also used antibodies against neutrophils (Gr-1) or CXCL2 receptor, CXCR2, to deplete neutrophils or to block the action of neutrophil chemokines to affirm their hypothesis.
帕加诺·M·B、巴托利·M·A、恩尼斯·T·L等人所著《二肽基肽酶I在实验性腹主动脉瘤形成过程中对中性粒细胞募集的关键作用》，发表于《美国国家科学院院刊》104(8)，2855 - 2860页（2007年）。在本研究中，作者使用二肽基肽酶I（DPPI）基因敲除小鼠以及主动脉弹性蛋白酶灌注诱导的小鼠腹主动脉瘤（AAA）模型，来研究DPPI（也称为组织蛋白酶C）在AAA形成过程中的作用。缺乏这种蛋白酶的小鼠对AAA形成具有抗性。有趣的是，这些作者发现DPPI活性控制中性粒细胞向炎症部位的募集，在此病例中具体为AAA病变部位。通过产生趋化因子CXCL2，AAA病变部位的中性粒细胞将更多中性粒细胞募集到病变部位，在这些部位这些细胞利用DPPI激活中性粒细胞丝氨酸蛋白酶，包括中性粒细胞弹性蛋白酶、组织蛋白酶G和蛋白酶3，这些蛋白酶可能进一步用于刺激巨噬细胞细胞因子和趋化因子的产生。除了DPPI缺陷小鼠外，作者还使用抗中性粒细胞（Gr - 1）或CXCL2受体CXCR2的抗体来耗尽中性粒细胞或阻断中性粒细胞趋化因子的作用，以证实他们的假设。
