Analysis of human blood monocyte activation at the level of gene expression: expression of alpha interferon genes during activation of human monocytes by poly IC/LC and muramyl dipeptide

• Published in: The Journal of experimental medicine Vol. 161; no. 3; pp. 503 - 513
• Main Authors: STEVENSON, H. C, DEKABAN, G. A, MILLER, P. J, CHEEPTIP BENYAJATI, PEARSON, M. L
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01-03-1985; The Rockefeller University Press
• Subjects: Acetylmuramyl-Alanyl-Isoglutamine - pharmacology; Biological and medical sciences; Carboxymethylcellulose Sodium - pharmacology; Cloning, Molecular; Cytoplasm - metabolism; DNA - metabolism; Fibroblast Growth Factors - biosynthesis; Fundamental and applied biological sciences. Psychology; Humans; Interferon Type I - biosynthesis; Interferon Type I - genetics; Macrophage Activation; Methylcellulose - analogs & derivatives; Microbiology; Monocytes - immunology; Monocytes - metabolism; Peptides - pharmacology; Poly I-C - pharmacology; Polylysine - pharmacology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; RNA, Messenger - isolation & purification; Virology; Human; Activation; Monocyte; Gene expression; Alpha interferon; Production
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.161.3.503

Human monocytes were activated to secrete alpha interferon (IFN-alpha) by poly IC/LC but not by other monocyte activators, such as muramyl dipeptide (MDP). In contrast, monocytes were activated to secrete fibroblast growth factor (FGF) release by MDP but not by poly IC/LC. The amount of total RNA present in unactivated and activated human monocytes was similar. Using two 32P-labeled cDNA probes (pLM001 and HuIFN-alpha 2) for human IFN-alpha genes in hybridization studies, we analyzed messenger RNA species from this gene family in activated human monocytes. After activation with poly IC/LC, two other mRNA species (2.8 and 5.5 kb) were detected in addition to the 1.0 kb mRNA normally associated with IFN-alpha secretion. Unexpectedly, monocytes activated with MDP also contained 2.8 kb IFN-alpha mRNA. There was associated with this 2.8 kb IFN-alpha mRNA, found in MDP-activated monocytes, appreciable levels of intracellular IFN-alpha activity in the absence of detectable secreted IFN-alpha. Thus the secretion of IFN-alpha in activated human monocytes can be correlated with the appearance of a 1.0 kb mRNA species after poly IC/LC exposure. Secretion appears to be defective in MDP-stimulated monocytes even though they contain active intracellular IFN-alpha apparently translated from the 2.8 kb mRNA.