The ability to modify responses to type I interferons (IFNs) could alter processes such as hematopoiesis and immunity, which involve endogenous IFNs and responses to exogenous IFNs. The data presented here support a significant role for a recently identified soluble isoform of the murine type I IFN receptor, muIfnar2a, as an efficient regulator of IFN responses. The messenger RNA (mRNA) transcript encoding muIfnar-2a is generally more abundant than that encoding the transmembrane isoform, muIfnar-2c. Furthermore, the ratio of muIfnar-2a:2c transcripts varied from more than 10:1 in the liver and other organs to less than 1:1 in bone-marrow macrophages, indicating independent regulation of the 2 transcripts encoding receptor isoforms and suggesting that the soluble muIfnar-2a levels are biologically relevant in some organs. Western blot analysis showed that soluble muIfnar-2 was present at high levels in murine serum and other biologic fluids and bound type I IFN. Recombinant muIfnar-2a competitively inhibited the activity of both IFN␣ and  in reporter assays using the L929 cell line and in antiproliferative and antiviral assays using primary cells. Surprisingly, IntroductionThe type I interferons (IFNs) are a family of cytokines produced in physiologic and pathologic conditions. Their biologic activities include inhibition of macrophage and lymphocyte proliferation, differentiation of macrophages, activation of natural killer and dendritic cells, and increased survival of memory T cells in addition to their well-characterized antiviral and antitumor activities. [1][2][3][4][5][6] These activities make type I IFNs important mediators of physiologic processes and disease pathogenesis and useful in the treatment of viral infections, some cancers (particularly those of hematopoietic origin), and other diseases, including multiple sclerosis. 7 In both human and mouse, the type I IFNs include multiple IFN␣ subtypes with about 75% to 99% amino acid identity and a single IFN with about 30% amino acid identity to IFN␣. 8 All type I IFNs have similar biologic activities and compete for binding to a common cell surface receptor. 9 The type I IFN receptor is composed of 2 known subunits: IFNAR-1 10 and IFNAR-2. 11 In humans and mice, there is a single form of IFNAR-1. 12 In contrast, multiple isoforms of human IFNAR-2 have been shown to result from alternative splicing of the same gene producing huIFNAR-2a (encoding a putative soluble isoform), huIFNAR-2b (encoding a putative transmembrane receptor with a truncated cytoplasmic domain), and huIFNAR-2c (encoding a putative full-length transmembrane receptor). 13 HuIFNAR-2c reconstituted IFN signaling in the huIFNAR-2-deficient cell line (U5A), which was otherwise unresponsive to IFN, whereas huIFNAR-2b did not, indicating that the latter was a nonfunctional isoform. 13 We recently cloned the murine orthologue of IFNAR-2 (muIfnar-2) and identified complementary DNAs (cDNAs) encoding full-length muIfnar-2c and soluble muIfnar-2a isoforms. 14 Northern blots showed 2 transcript...
Resistance to a range of heavy metal ions was determined for lead-resistant and other bacteria which had been isolated from a battery-manufacturing site contaminated with high concentration of lead. Several Gram-positive (belonging to the genera Arthrobacter and Corynebacterium) and Gram-negative (Alcaligenes species) isolates were resistant to lead, mercury, cadmium, cobalt, zinc and copper, although the levels of resistance to the different metal ions were specific for each isolate. Polymerase chain reaction, DNA-DNA hybridization and DNA sequencing were used to explore the nature of genetic systems responsible for the metal resistance in eight of the isolates. Specific DNA sequences could be amplified from the genomic DNA of all the isolates using primers for sections of the mer (mercury resistance determinant on the transposon Tn501) and pco (copper resistance determinant on the plasmid pRJ1004) genetic systems. Positive hybridizations with mer and pco probes indicated that the amplified segments were highly homologous to these genes. Some of the PCR products were cloned and partially sequenced, and the regions sequenced were highly homologous to the appropriate regions of the mer and pco determinants. These results demonstrate the wide distribution of mercury and copper resistance genes in both Gram-positive and Gram-negative isolates obtained from this lead-contaminated soil. In contrast, the czc (cobalt, zinc and cadmium resistance) and chr (chromate resistance) genes could not be amplified from DNAs of some isolates, indicating the limited contribution, if any, of these genetic systems to the metal ion resistance of these isolates.
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