Title

Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma

UMMS Affiliation

Department of Pediatrics

Publication Date

7-1-1988

Document Type

Article

Subjects

Cytochrome b Group; *Gene Expression Regulation; Humans; Interferon Type I; Interferon Type II; Leukemia, Myeloid; Macrophages; Neutrophils; Phagocytes; Recombinant Proteins; Superoxides; Transcription, Genetic; Tumor Cells, Cultured

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 1988 Jul;85(14):5215-9.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

2839835