Different Isoforms of the Neuronal Guidance Molecule Slit2 Directly Cause Chemoattraction or Chemorepulsion of Human Neutrophils.
Different Isoforms of the Neuronal Guidance Molecule Slit2 Directly Cause Chemoattraction or Chemorepulsion of Human Neutrophils.
复制标题
DOI：
10.4049/jimmunol.1800681
复制
发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Gomer RH
中科院分区：
文献类型：
--
作者：
Pilling D;Chinea LE;Consalvo KM;Gomer RH
中性粒细胞在血液和组织之间的运动似乎受到化学引诱剂和化学排斥剂的调节。与中性粒细胞化学引诱剂相比，对中性粒细胞化学排斥剂的了解相对较少。Slit蛋白被内源性切割成各种N和C末端片段，并且这些片段是神经元化学排斥剂并且抑制许多细胞类型（包括嗜中性粒细胞）的化学吸引。在这份报告中，我们表明，140 kDa的N-末端Slit 2片段（Slit 2-N）是一种化学引诱剂和110 kDa的N-末端Slit 2片段（Slit 2-S）是人类中性粒细胞的化学排斥剂。两个Slit 2片段的作用被Slit 2受体Robo 1或Slit 2共受体多配体聚糖-4的抗体阻断。Slit 2-N似乎没有激活Ras，但增加了PIP 3水平。Slit 2-N诱导的趋化作用不受Ras抑制剂的影响，被PI 3激酶抑制剂逆转，并被Cdc 42和Rac抑制剂阻断。相反，Slit 2-S激活Ras但不增加PIP 3水平。Slit 2-S诱导的化学排斥可被Ras和Rac抑制剂阻断，而不受PI 3激酶抑制剂的影响，并可被cdc 42抑制剂逆转。Slit 2-N而不是Slit 2-S增加了中性粒细胞粘附，肌球蛋白II轻链磷酸化，极化肌动蛋白形成和细胞前缘的单伪足。Slit 2-S诱导多个伪足。这些数据表明，Slit-2亚型使用相似的受体，但不同的细胞内信号传导途径，并有不同的影响，对细胞骨架和伪足，诱导中性粒细胞化学吸引或化学排斥。
The movement of neutrophils between blood and tissues appears to be regulated by chemoattractants and chemorepellents. Compared to neutrophil chemoattractants, relatively little is known about neutrophil chemorepellents. Slit proteins are endogenously cleaved into a variety of N and C terminal fragments, and these fragments are neuronal chemorepellents and inhibit chemoattraction of many cell types, including neutrophils. In this report, we show that the 140 kDa N-terminal Slit2 fragment (Slit2-N) is a chemoattractant and the 110 kDa N-terminal Slit2 fragment (Slit2-S) is a chemorepellent for human neutrophils. The effects of both Slit2 fragments were blocked by antibodies to the Slit2 receptor Robo1 or the Slit2 co-receptor syndecan-4. Slit2-N did not appear to activate Ras, but increased PIP3 levels. Slit2-N induced chemoattraction was unaffected by Ras inhibitors, reversed by PI3 kinase inhibitors, and blocked by cdc42 and Rac inhibitors. In contrast, Slit2-S activated Ras but did not increase PIP3 levels. Slit2-S induced chemorepulsion was blocked by Ras and Rac inhibitors, not affected by PI3 kinase inhibitors, and was reversed by cdc42 inhibitors. Slit2-N but not Slit2-S increased neutrophil adhesion, myosin II light chain phosphorylation, and polarized actin formation and single pseudopods at the leading edge of cells. Slit2-S induced multiple pseudopods. These data suggest that Slit-2 isoforms use similar receptors but different intracellular signaling pathways, and have different effects on the cytoskeleton and pseudopods, to induce neutrophil chemoattraction or chemorepulsion.
登录
查看更多内容
影响因子：
64.8
作者：
LI, N;BATZER, A;SCHLESSINGER, J
通讯作者：
SCHLESSINGER, J
影响因子：
20.3
作者：
Dunzendorfer, S;Kaneider, N;Wiedermann, CJ
通讯作者：
Wiedermann, CJ
影响因子：
25
作者：
Delloye-Bourgeois, Celine;Jacquier, Arnaud;Castellani, Valerie
通讯作者：
Castellani, Valerie
影响因子：
10.4
作者：
Duetting, S.;Heidenreich, J.;Nieswandt, B.
通讯作者：
Nieswandt, B.
影响因子：
3.9
作者：
Hohenester, Erhard
通讯作者：
Hohenester, Erhard