Quantum proteolytic activation of chemokine CCL15 by neutrophil granulocytes modulates mononuclear cell adhesiveness
Quantum proteolytic activation of chemokine CCL15 by neutrophil granulocytes modulates mononuclear cell adhesiveness
复制标题
DOI：
10.4049/jimmunol.175.3.1599
复制
发表时间：
2005-08-01
影响因子：
4.4
通讯作者：
Forssmann, U
中科院分区：
文献类型：
--
作者：
Richter, R;Bistrian, R;Forssmann, U
单核细胞浸润到炎症部位之前通常是中性粒细胞。我们在这里表明，中性粒细胞可能通过激活CCL15（一种在血浆中循环的人类趋化因子）来支持这一过程。发现中性粒细胞在肾功能不全患者血液滤过过程中释放CCL15蛋白水解活性。CCL15免疫反应性（IR）在细胞周围空间的处理表明血液和血液滤液中缺乏蛋白水解活性，但CCL15-IR的保留时间（t(R)）发生了变化，通过色谱分离血液和血液滤液中CCL15-IR检测。经鉴定，n端缺失23 （Delta 23）和26 (Delta 26) aa的CCL15分子是血液滤过液的主要蛋白水解产物。中性粒细胞组织蛋白酶G是产生δ 23和δ 26 CCL15的主要蛋白酶。此外，弹性蛋白酶显示CCL15蛋白水解活性并产生Delta 21异构体。与全长CCL15相比，Delta 23和Delta 26亚型在诱导钙通量和单核细胞趋化活性以及诱导单核细胞粘附纤维连接蛋白方面表现出显著增强的效力。因此，我们的研究结果表明，嗜中性粒细胞对单核细胞的激活至少部分是由嗜中性粒细胞组织蛋白酶G对循环或内皮结合的CCL15进行量子蛋白水解处理诱导的。
Monocyte infiltration into inflammatory sites is generally preceded by neutrophils. We show here that neutrophils may support this process by activation of CCL15, a human chemokine circulating in blood plasma. Neutrophils were found to release CCL15 proteolytic activity in the course of hemofiltration of blood from renal insufficiency patients. Processing of CCL15 immunoreactivity (IR) in the pericellular space is suggested by a lack of proteolytic activity in blood and blood filtrate, but a shift of the retention time (t(R)) of CCL15-IR, detected by chromatographic separation of CCL15-IR in blood and hemofiltrate. CCL15 molecules with N-terminal deletions of 23 (Delta 23) and 26 (Delta 26) aa were identified as main proteolytic products in hemofiltrate. Neutrophil cathepsin G was identified as the principal protease to produce Delta 23 and Delta 26 CCL15. Also, elastase displays CCL15 proteolytic activity and produces a Delta 21 isoform. Compared with full-length CCL15, Delta 23 and Delta 26 isoforms displayed a significantly increased potency to induce calcium fluxes and chemotactic activity on monocytes and to induce adhesiveness of mononuclear cells to fibronectin. Thus, our findings indicate that activation of monocytes by neutrophils is at least in part induced by quantum proteolytic processing of circulating or endothelium-bound CCL15 by nentrophil cathepsin G.