The Journal of Immunology, Vol 141, Issue 1 180-188, Copyright © 1988 by American Association of Immunologists

ARTICLES

Differential regulation of gene expression during macrophage activation with a polyribonucleotide. The role of endogenously derived IFN

DW Riches, PM Henson, LK Remigio, JF Catterall and RC Strunk
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.

The activation of macrophages by exposure to the polyribonucleotide, poly [I:C], is accompanied by a large stimulation of the synthesis of the C components factor B and C3, and a concomitant inhibition of the synthesis of the lysosomal enzyme beta-glucuronidase. Northern blot analysis of poly [A+] RNA extracted from poly [I:C]-stimulated cells revealed that the changes in the synthesis of factor B and C3 were related to changes in the levels of their respective mRNA and hence the expression of these proteins appeared to be regulated at a pre- translational level. The down-regulation of the synthesis of beta- glucuronidase appeared to be regulated at both translational and pre- translational levels. In view of the proposed role of macrophage- derived IFN in the regulation of macrophage activation, we investigated the possible role of IFN-alpha/beta in the regulation of the synthesis of factor B, C3, and beta-glucuronidase. Exposure of macrophages to mouse IFN-alpha and IFN-beta induced limited changes in the synthesis of factor B, C3, and beta-glucuronidase. However, pretreatment of macrophages with only 500 U/ml of IFN-beta primed the cells thereby increasing their sensitivity to poly [I:C]. IFN-alpha was less effective as a priming agent. When macrophages were exposed to poly [I:C] in the presence of an anti-mouse IFN-alpha/beta antiserum, the changes in the synthesis of factor B, C3, and beta-glucuronidase were partially inhibited. Collectively, these data indicate first, that exposure of mouse bone marrow-derived macrophages to poly [I:C] differentially regulates the expression of the products of the genes for factor B, C3, and beta-glucuronidase. Second, IFN-alpha and IFN- beta prime macrophages to increase the sensitivity of macrophages to poly [I:C]. Third, in the absence of exogenous IFN, macrophage-derived IFN appears to participate in priming the cells in an autocrine or paracrine fashion.

This article has been cited by other articles:

				E. A. Eugenin, M. C. Branes, J. W. Berman, and J. C. Saez TNF-{alpha} Plus IFN-{gamma} Induce Connexin43 Expression and Formation of Gap Junctions Between Human Monocytes/Macrophages That Enhance Physiological Responses J. Immunol., February 1, 2003; 170(3): 1320 - 1328. [Abstract] [Full Text] [PDF]

				M. Saio, S. Radoja, M. Marino, and A. B. Frey Tumor-Infiltrating Macrophages Induce Apoptosis in Activated CD8+ T Cells by a Mechanism Requiring Cell Contact and Mediated by Both the Cell-Associated Form of TNF and Nitric Oxide J. Immunol., November 15, 2001; 167(10): 5583 - 5593. [Abstract] [Full Text] [PDF]

				V. A. Fadok, D. L. Bratton, L. Guthrie, and P. M. Henson Differential Effects of Apoptotic Versus Lysed Cells on Macrophage Production of Cytokines: Role of Proteases J. Immunol., June 1, 2001; 166(11): 6847 - 6854. [Abstract] [Full Text] [PDF]

				T. Fournier, V. Fadok, and P. M. Henson Tumor Necrosis Factor-alpha Inversely Regulates Prostaglandin D2 and Prostaglandin E2 Production in Murine Macrophages. SYNERGISTIC ACTION OF CYCLIC AMP ON CYCLOOXYGENASE-2 EXPRESSION AND PROSTAGLANDIN E2 SYNTHESIS J. Biol. Chem., December 5, 1997; 272(49): 31065 - 31072. [Abstract] [Full Text] [PDF]

				V. A. Fadok, A. de Cathelineau, D. L. Daleke, P. M. Henson, and D. L. Bratton Loss of Phospholipid Asymmetry and Surface Exposure of Phosphatidylserine Is Required for Phagocytosis of Apoptotic Cells by Macrophages and Fibroblasts J. Biol. Chem., January 5, 2001; 276(2): 1071 - 1077. [Abstract] [Full Text] [PDF]