Differential regulation of gene expression during macrophage activation with a polyribonucleotide. The role of endogenously derived IFN.
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.
Riches
D W
DW
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Henson
P M
PM
Remigio
L K
LK
Catterall
J F
JF
Strunk
R C
RC
D000818:Animals; D003176:Complement C3 / Q000096:biosynthesis / Q000235:genetics; D011415:Complement Factor B / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D005966:Glucuronidase / Q000096:biosynthesis / Q000235:genetics; D007106:Immune Sera / Q000494:pharmacology; D007370:Interferon Type I / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009500:Neutralization Tests; D011070:Poly I-C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
D003176:Complement C3; D007106:Immune Sera; D007370:Interferon Type I; D012333:RNA, Messenger; D005966:Glucuronidase; D011415:Complement Factor B; D011070:Poly I-C