Newburger P E, Ezekowitz R A, Whitney C, Wright J, Orkin S H
Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655.
Proc Natl Acad Sci U S A. 1988 Jul;85(14):5215-9. doi: 10.1073/pnas.85.14.5215.
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, phagocyte 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.
吞噬细胞，如巨噬细胞和多形核白细胞，会产生“呼吸爆发”，在此过程中氧气被还原为超氧化物和其他活性氧物质，这些物质负责这些细胞的许多杀菌、杀肿瘤和炎症活动。γ干扰素已被证明可增强吞噬细胞超氧化物的产生，但其作用的分子机制尚不清楚。最近，氧化酶的一个关键成分——吞噬细胞细胞色素b，已被鉴定为一种91 kDa糖蛋白和一种22 kDa多肽的异二聚体。本研究检测了重组人γ干扰素对细胞色素b这些成分基因表达的影响。用γ干扰素进行体外处理可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重链基因转录本的水平。轻链基因转录本受影响较小。在单核细胞衍生的巨噬细胞和THP-1细胞中，重链基因表达的增强在很大程度上归因于转录速率的增加。用人重组α干扰素（呼吸爆发的下调因子）处理单核细胞衍生的巨噬细胞会降低重链转录本水平；β干扰素未产生可检测到的变化。这些发现证明了吞噬细胞氧化酶系统的一个重要成分对γ干扰素激活的反应性，并为其在慢性肉芽肿病中增强吞噬功能的应用提供了理论依据。
