SHIP-1 Increases Early Oxidative Burst and Regulates Phagosome Maturation in Macrophages1
SHIP-1 Increases Early Oxidative Burst and Regulates Phagosome Maturation in Macrophages1
复制标题
SHIP-1 增加早期氧化爆发并调节巨噬细胞中吞噬体的成熟1
作者：
Lynn Kamen;J. Levinsohn;Amy M Cadwallader;S. Tridandapani;J. Swanson
虽然肌醇磷酸酶SHIP-1通常被认为抑制Fc受体介导的吞噬作用的信号传导，但其活性产物磷脂酰肌醇3,4二磷酸（PI(3,4)P2）与NADPH氧化酶的激活有关。这表明SHIP-1正调控吞噬后活性氧的产生。为了研究SHIP-1活性如何促进Fc受体介导的吞噬，我们测量并比较了SHIP-1缺陷小鼠和野生型小鼠巨噬细胞的磷脂动力学、膜运输和氧化破裂。ship -1缺陷巨噬细胞吞噬体膜上PI(3,4,5)P3与PI(3,4)P2的比值显著升高。吞噬体中活性氧中间体活性成像显示ship -1缺陷巨噬细胞早期NADPH氧化酶活性降低。SHIP-1缺陷也改变了吞噬体成熟的后期阶段，这可以从PI(3)P的持续升高和Rab5a早期定位到吞噬体中得到证实。这些对单个细胞器的直接测量表明，吞噬体SHIP-1通过局部改变膜3 ' -磷酸肌肽组成来增强早期氧化爆发。
Although the inositol phosphatase SHIP-1 is generally thought to inhibit signaling for Fc receptor-mediated phagocytosis, the product of its activity, phosphatidylinositol 3,4 bisphosphate (PI(3,4)P2), has been implicated in activation of the NADPH oxidase. This suggests that SHIP-1 positively regulates the generation of reactive oxygen species after phagocytosis. To examine how SHIP-1 activity contributes to Fc receptor-mediated phagocytosis, we measured and compared phospholipid dynamics, membrane trafficking, and the oxidative burst in macrophages from SHIP-1-deficient and wild-type mice. SHIP-1-deficient macrophages showed significantly elevated ratios of PI(3,4,5)P3 to PI(3,4)P2 on phagosomal membranes. Imaging reactive oxygen intermediate activities in phagosomes revealed decreased early NADPH oxidase activity in SHIP-1-deficient macrophages. SHIP-1 deficiency also altered later stages of phagosome maturation, as indicated by the persistent elevation of PI(3)P and the early localization of Rab5a to phagosomes. These direct measurements of individual organelles indicate that phagosomal SHIP-1 enhances the early oxidative burst through localized alteration of the membrane 3′-phosphoinositide composition.
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影响因子：
3.3
作者：
Hoppe, AD;Swanson, JA
通讯作者：
Swanson, JA
DOI：
10.1073/pnas.93.4.1689
发表时间：
1996-02-20
影响因子：
11.1
作者：
Damen, JE;Liu, L;Krystal, G
通讯作者：
Krystal, G
巨噬细胞中管状溶酶体室的可塑性。
影响因子：
4
作者：
Knapp,PE;Swanson,JA
通讯作者：
Swanson,JA
影响因子：
3.4
作者：
Hoppe, A;Christensen, K;Swanson, JA
通讯作者：
Swanson, JA