Lymphocytic 2',5'-oligoadenylate synthetase is insensitive to dsRNA and interferon stimulation in autoimmune BB rats.
The interferon (IFN)-dependent 2',5'-oligoadenylate synthetase (2-5A synthetase), which produces 2',5'-oligoadenylates from ATP, was analyzed in homogenates of isolated peripheral blood lymphocytes (PBL) from BB and Sprague-Dawley rats, man, sheep, and beagle dog. In all the examined species, the 2-5A synthetase was expressed constitutively and showed sensitivity differences to poly(I:C) (synthetic dsRNA). The 2-5A synthetase activity in the absence of poly(I:C) was high in the BB and Sprague-Dawley rat where only 2-5A dimers were synthesized. With the notable exception of PBL homogenates from BB rats, increasing poly(I:C) concentrations resulted in an increased 2-5A synthetase activity leading to the production of higher 2-5A oligomers, predominantly the octamer. Diabetes-resistant, diabetes-prone, and diabetic BB rats were indistinguishable in that their 2-5A synthetase was insensitive to poly(I:C). Preincubation of PBL from BB and Sprague-Dawley rats with up to 1,000 U/ml rat IFN elicited a moderate increase of 60% in the activity level of 2-5A synthetase. In contrast, preincubation of human PBL with human IFN-alpha led as expected to a 300% increase in 2-5A activity. Thus, the BB rat was markedly different from the other species in producing only the biologically inactive 2-5A dimers and in having a high basal 2-5A synthetase activity, that was unaffected by poly(I:C). We believe that these factors per se or together may render the BB rat more susceptible to virus attacks and/or may create a background that will facilitate the development of autoimmune processes.
Bonnevie-Nielsen
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Department of Clinical Chemistry, Odense University Hospital, Denmark.
Husum
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Kristiansen
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K
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000276:immunology; D004195:Disease Models, Animal; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008214:Lymphocytes / Q000201:enzymology*; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D051381:Rats; D011913:Rats, Inbred BB; D011919:Rats, Inbred Strains; D012756:Sheep
D016898:Interferon-alpha; D012330:RNA, Double-Stranded; D015088:2',5'-Oligoadenylate Synthetase; D011070:Poly I-C