Kidney injury enhances renal G‐CSF expression and modulates granulopoiesis and human neutrophil CD177 in vivo
Kidney injury enhances renal G‐CSF expression and modulates granulopoiesis and human neutrophil CD177 in vivo
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肾损伤增强肾 G-CSF 表达并调节体内粒细胞生成和人中性粒细胞 CD177
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发表时间：
2019
影响因子：
4.6
通讯作者：
S. von Vietinghoff
中科院分区：
文献类型：
--
作者：
J. Volkmann;J. Schmitz;J. Nordlohne;L. Dong;A. Helmke;P. Sen;S. Immenschuh;W. Bernhardt;W. Gwinner;J. Bräsen;R. Schmitt;H. Haller;S. von Vietinghoff
肾脏损伤显著增加了总体死亡率。中性粒细胞是人类血液中含量最丰富的白细胞。它们的特点是周转率高，主要受粒细胞集落刺激因子(G-CSF)控制。肾损伤和尿毒症在粒细胞生成调节中的作用尚未见报道。肾移植本身就会引起移植物的缺血再灌注损伤，使人中性粒细胞表面糖蛋白CD177表达升高。CD177是对G-CSF反应最强的中性粒细胞基因之一，在接受重组G-CSF的健康供者的中性粒细胞上可逆地增加。在肾移植受者中，中性粒细胞CD177的一过性升高与肾小管上皮细胞G-CSF表达相关。相比之下，CD177在慢性肾损害患者中没有改变，并且独立于肾脏替代治疗。在小鼠实验性缺血再灌注和单侧输尿管梗阻损伤的受控条件下，肾脏G-CSF的mRNA和蛋白表达显著增加，并出现全身性中性粒细胞减少。体外培养的人肾小管上皮细胞经低氧和促炎细胞因子IL-17A刺激后，G-CSF表达增强。临床上，ABO血型不合的肾移植受者中性粒细胞CD177的升高幅度更大。他们的移植物的特点是补体C4D沉积在肾内皮细胞上，即使在没有排斥反应的情况下也是如此。事实上，补体激活，而不是缺氧，诱导了原代人内皮细胞G-CSF的表达。我们的数据表明，肾脏损伤诱导了肾脏G-CSF的表达并调节了粒细胞的生成。他们描述了肾上皮和内皮细胞中G-CSF的不同调节。粒细胞生成改变可能导致肾脏损伤的全身性影响。
Kidney injury significantly increases overall mortality. Neutrophilic granulocytes (neutrophils) are the most abundant human blood leukocytes. They are characterized by a high turnover rate, chiefly controlled by granulocyte colony stimulating factor (G‐CSF). The role of kidney injury and uremia in regulation of granulopoiesis has not been reported. Kidney transplantation, which inherently causes ischemia–reperfusion injury of the graft, elevated human neutrophil expression of the surface glycoprotein CD177. CD177 is among the most G‐CSF‐responsive neutrophil genes and reversibly increased on neutrophils of healthy donors who received recombinant G‐CSF. In kidney graft recipients, a transient rise in neutrophil CD177 correlated with renal tubular epithelial G‐CSF expression. In contrast, CD177 was unaltered in patients with chronic renal impairment and independent of renal replacement therapy. Under controlled conditions of experimental ischemia–reperfusion and unilateral ureteral obstruction injuries in mice, renal G‐CSF mRNA and protein expression significantly increased and systemic neutrophilia developed. Human renal tubular epithelial cell G‐CSF expression was promoted by hypoxia and proinflammatory cytokine interleukin 17A in vitro. Clinically, recipients of ABO blood group‐incompatible kidney grafts developed a larger rise in neutrophil CD177. Their grafts are characterized by complement C4d deposition on the renal endothelium, even in the absence of rejection. Indeed, complement activation, but not hypoxia, induced primary human endothelial cell G‐CSF expression. Our data demonstrate that kidney injury induces renal G‐CSF expression and modulates granulopoiesis. They delineate differential G‐CSF regulation in renal epithelium and endothelium. Altered granulopoiesis may contribute to the systemic impact of kidney injury.
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影响因子：
20.3
作者：
Bai, Ming;Grieshaber-Bouyer, Ricardo;Nigrovic, Peter A.
通讯作者：
Nigrovic, Peter A.
影响因子：
8
作者：
Carlucci, Philip M.;Purmalek, Monica M.;Kaplan, Mariana J.
通讯作者：
Kaplan, Mariana J.
影响因子：
19.6
作者：
Noone DG;Riedl M;Pluthero FG;Bowman ML;Liszewski MK;Lu L;Quan Y;Balgobin S;Schneppenheim R;Schneppenheim S;Budde U;James P;Atkinson JP;Palaniyar N;Kahr WH;Licht C
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Licht C
双转基因中性粒细胞方法诱导小鼠抗蛋白酶 3 抗体介导的血管炎的经验教训
影响因子：
5.5
作者：
Schreiber A;Eulenberg-Gustavus C;Bergmann A;Jerke U;Kettritz R
通讯作者：
Kettritz R
影响因子：
4.8
作者：
Helmke, Alexandra;Casper, Janis;von Vietinghoff, Sibylle
通讯作者：
von Vietinghoff, Sibylle