期刊
JOURNAL OF IMMUNOLOGY
卷 180, 期 11, 页码 7497-7505出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.11.7497
关键词
-
类别
资金
- NCI NIH HHS [P01 CA095426] Funding Source: Medline
- NIAID NIH HHS [R01 AI035950-15, R21 AI035950, R01 AI064668-04, AI35950, R01 AI035950, AI64668, R01 AI064668] Funding Source: Medline
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)P-2), 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)P-3 to PI(3,4)P-2 on phagosomal membranes. Imaging reactive oxygen intermediate activities in phagosomes revealed decreased early NADPH oxidase activity in SHIP-I-deficient macrophages. SHIP-I 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据