Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms.
Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms.
复制标题
DOI：
10.1111/j.1600-0854.2009.01029.x
复制
发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Catz SD
中科院分区：
文献类型：
--
作者：
Johnson JL;Brzezinska AA;Tolmachova T;Munafo DB;Ellis BA;Seabra MC;Hong H;Catz SD
中性粒细胞依靠胞吐作用调动受体和粘附分子，释放杀微生物因子。这一过程应受到严格控制，因为不受控制的有毒蛋白质释放会对宿主造成伤害。体内研究表明，小GTPase Rab27a调节嗜氮颗粒胞吐。利用Rab27a （Rab27aash/ash）、Rab27b （Rab27b敲除）或两者都缺失（Rab27a/b双KO）的小鼠中性粒细胞，我们研究了Rab27亚型在中性粒细胞中的作用。我们发现Rab27a和Rab27b缺陷都会损害嗜氮颗粒胞吐。Rab27aash/灰中性粒细胞显示Rab27b表达上调，但这并不能弥补rab27a缺陷细胞中观察到的分泌缺陷，这表明Rab27亚型在中性粒细胞胞吐作用中起独立作用。全内反射荧光显微镜分析显示，Rab27aash/ash和Rab27b敲除中性粒细胞在质膜附近的亲氮颗粒数量减少。在Rab27a/b双KO中性粒细胞中，这种作用加剧。缺乏rab27的中性粒细胞显示出质膜上NADPH氧化酶的激活受损，但噬菌体内ROS的产生不受影响。缺乏Rab27的中性粒细胞分泌囊泡的胞吐功能正常，提示Rab27 gtpase选择性控制中性粒细胞颗粒的胞吐。
Neutrophils rely on exocytosis to mobilize receptors and adhesion molecules and to release microbicidal factors. This process should be strictly regulated because uncontrolled release of toxic proteins would be injurious to the host. In vivo studies showed that the small GTPase Rab27a regulates azurophilic granule exocytosis. Using mouse neutrophils deficient in Rab27a (Rab27aash/ash), Rab27b (Rab27b knockout) or both (Rab27a/b double KO), we investigated the role of the Rab27 isoforms in neutrophils. We found that both Rab27a and Rab27b deficiencies impaired azurophilic granule exocytosis. Rab27aash/ash neutrophils showed upregulation of Rab27b expression which did not compensate for the secretory defects observed in Rab27a-deficient cells suggesting that Rab27 isoforms play independent roles in neutrophil exocytosis. Total internal reflection fluorescence microscopy analysis showed that Rab27aash/ash and Rab27b knockout neutrophils have a decreased number of azurophilic granules near the plasma membrane. The effect was exacerbated in Rab27a/b double KO neutrophils. Rab27-deficient neutrophils, showed impaired activation of the NADPH oxidase at the plasma membrane although intraphagosomal ROS production was not affected. Exocytosis of secretory vesicles in Rab27-deficient neutrophils was functional, suggesting that Rab27 GTPases selectively control the exocytosis of neutrophil granules.
登录
查看更多内容
影响因子：
5.9
作者：
GRISCELLI, C;DURANDY, A;PRUNIERAS, M
通讯作者：
PRUNIERAS, M
影响因子：
3.3
作者：
Gomi, Hiroshi;Mori, Kenichi;Izumi, Tetsuro
通讯作者：
Izumi, Tetsuro
影响因子：
4
作者：
Imai, A;Yoshie, S;Fukuda, M
通讯作者：
Fukuda, M
影响因子：
3
作者：
Johnson, Jennifer L.;Ellis, Beverly A.;Catz, Sergio D.
通讯作者：
Catz, Sergio D.
影响因子：
15.9
作者：
Barral, DC;Ramalho, JS;Seabra, MC
通讯作者：
Seabra, MC