Production of interferon-alpha induced by dsRNA in human peripheral blood mononuclear cell cultures: role of priming by dsRNA-induced interferons-gamma and -beta.
Poly(I):poly(C) (rIn.rCn), mismatched poly(I):poly(C) [rIn.r(C12U)n], and poly(I):poly(C) poly-lysine carboxymethylcellulose [poly(ICLC)] were studied for their capacity to induce interferon-alpha (IFN-alpha) in human peripheral blood mononuclear cell (MNC) cultures and in their subpopulations. In MNC, poly(I):poly(C) and mismatched poly(I):poly(C) induced IFN-alpha in a dose-dependent manner, whereas poly(ICLC) was unable to do so in concentrations that ranged from 1 to 160 micrograms/ml. In contrast, all three molecules were incapable of inducing IFN-alpha when added into either purified monocyte or lymphocyte cultures. The capacity of poly(I):poly(C) to induce IFN-alpha was reestablished only in monocyte cultures when, prior to the stimulation, the cells were exposed for at least 2 h to supernatants from poly(I):poly(C)-stimulated lymphocyte cultures. IFN-beta and IFN-gamma were found in those supernatants and the ability of each dsRNA to induce IFN-alpha correlated with its ability to induce IFN-gamma. Further studies using recombinant human IFN-gamma and IFN-beta and their specific antibodies corroborated an important role of these molecules for the induction of IFN-alpha with dsRNA. Because each IFN type is produced by different cells, our studies show that complex cell-to-cell interactions via other IFNs have to take place in peripheral blood mononuclear cells (MNC) cultures before IFN-alpha can be induced by dsRNA.
Lepe-Zuniga
J L
JL
Department of Clinical Immunology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Rotbein
J
J
Gutterman
J U
JU
D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology / Q000031:analogs & derivatives; D002478:Cells, Cultured; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000096:biosynthesis* / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D011072:Poly U; D011107:Polylysine / Q000494:pharmacology / Q000031:analogs & derivatives; D011131:Polyribonucleotides / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology*
D007369:Interferon Inducers; D007370:Interferon Type I; D011131:Polyribonucleotides; D012330:RNA, Double-Stranded; D011107:Polylysine; D011072:Poly U; C019531:poly ICLC; D007371:Interferon-gamma; C047490:poly(I).poly(c12,U); D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C