Macrophages are a critically important component of the innate and adaptive immune systems. They are equipped with oxidative and non-oxidative mechanisms to kill ingested pathogens. Natural Killer Lytic-Associated Molecule (NKLAM) is an E3 ubiquitin ligase expressed in macrophages and natural killer cells. We show that NKLAM expression in macrophages was enhanced by Toll-like receptor agonists and pro-inflammatory cytokines. Using confocal microscopy, we found that NKLAM colocalized with ingested Escherichia coli. In assays using IgG-opsonized latex beads as targets, we demonstrated that NKLAM translocated to the phagosome early during maturation at a time that coincided with elevated levels of ubiquitinated phagosome proteins. In killing assays with bone marrow-derived macrophages from wild type and NKLAM-deficient mice, we found that NKLAM-deficient macrophages demonstrated less killing of E. coli than wild type macrophages. Collectively, our data show that NKLAM is a novel component of macrophage phagosomes and is involved in macrophage bactericidal functions.

译文

巨噬细胞是先天和适应性免疫系统的至关重要的组成部分。它们配备了氧化和非氧化机制,可以杀死摄入的病原体。天然杀手液相关分子(NKLAM)是在巨噬细胞和天然杀手细胞中表达的E3泛素连接酶。我们显示,巨噬细胞中的NKLAM表达被Toll样受体激动剂和促炎性细胞因子增强。使用共聚焦显微镜,我们发现NKLAM与摄入的大肠杆菌共定位。在使用IgG调理乳胶珠作为靶标的测定中,我们证明了NKLAM在成熟过程中的早期就易位到吞噬体,而此时泛素化的吞噬体蛋白水平升高。在用野生型和NKLAM缺陷型小鼠的骨髓巨噬细胞进行的杀伤试验中,我们发现NKLAM缺陷型巨噬细胞对大肠杆菌的杀灭作用少于野生型巨噬细胞。总体而言,我们的数据表明NKLAM是巨噬细胞吞噬体的一种新型成分,并参与巨噬细胞的杀菌功能。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录