INDUCTION OF PHAGOCYTE CYTOCHROME-B HEAVY-CHAIN GENE-EXPRESSION BY INTERFERON-GAMMA
INDUCTION OF PHAGOCYTE CYTOCHROME-B HEAVY-CHAIN GENE-EXPRESSION BY INTERFERON-GAMMA
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DOI：
10.1073/pnas.85.14.5215
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发表时间：
1988-07-01
影响因子：
11.1
通讯作者：
ORKIN, SH
中科院分区：
文献类型：
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作者：
NEWBURGER, PE;EZEKOWITZ, RAB;ORKIN, SH
吞噬细胞，如巨噬细胞和多形核白细胞，产生“呼吸爆发”，其中氧被还原为超氧化物和其他活性氧物质，这些活性氧物质负责这些细胞的许多杀微生物、杀肿瘤和炎症活性。干扰素γ已经显示出增加吞噬细胞超氧化物的产生，但这种作用的分子机制仍然未知。最近的一个关键组成部分的氧化酶，吞噬细胞色素B，已被确定为一个异源二聚体的91 kDa的糖蛋白和22 kDa的多肽。本研究检测了人重组干扰素γ的作用。细胞色素B的这些成分的基因表达。用干扰素γ的体外治疗显著增加正常多形核白细胞、正常单核细胞衍生的巨噬细胞和单核细胞白血病细胞系THP-1中吞噬细胞细胞色素B重链基因转录物的水平。轻链基因转录物受影响较小。在单核细胞衍生的巨噬细胞和THP-1细胞中，重链基因的表达增强似乎在很大程度上归因于转录速率的增加。用人重组干扰素α治疗单核细胞衍生的巨噬细胞（呼吸爆发的下调因子）降低了重链转录物水平;没有产生可检测的变化。这些发现证实了吞噬细胞氧化酶系统的一种基本组分对干扰素γ激活的应答性。并提供了其用于增强慢性肉芽肿性疾病中的吞噬功能的基本原理。
Phagocytic cells, such as macrophages and polymorphonuclear leukocytes, produce a "respiratory burst" in which oxygen is reduced to superoxide and other active oxygen species responsible for many of the microbicidal, tumoricidal, and inflammatory activities of these cells. Interferon .gamma. has been shown to augment phagocyte superoxide production, but the molecular mechanisms underlying this effect have remained unknown. Recently a key component of the oxidase, phagocye cytochrome b, has been characterized as a heterodimer of a 91-kDa glycoprotein and a 22-kDa polypeptide. The present studies examined the effects of human recombinant interferon .gamma. on the expression of the genes for these components of the cytochrome b. In vitro treatment with interferon .gamma. substantially increases the level of phagocyte cytochrome b heavy chain gene transcripts in normal polymorphonuclear leukocytes, normal monocyte-derived macrophages, and the monocytic leukemia cell line THP-1. Light chain gene transcripts are less affected. In monocyte-derived macrophages and THP-1 cells, the enhanced expression of the heavy chain gene appears in large part attributable to increased rates of transcription. Treatment of monocyte-derived macrophages with human recombinant interferon .alpha. (a down-regulator of the respiratory burst) decreased the heavy chain transcript levels; interferon .beta. produced no detectable change. These findings demonstrate the responsiveness of one essential component of the phagocyte oxidase system to activation by interferon .gamma. and provide a rationale for its use to augment phagocytic function in chronic granulomatous disease.