Lymphocytic 2',5'-oligoadenylate synthetase is insensitive to dsRNA and interferon stimulation in autoimmune BB rats

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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.
Original languageEnglish
JournalJournal of Interferon Research
Issue number6
Pages (from-to)351-6
Number of pages5
Publication statusPublished - 1991
Externally publishedYes

Bibliographical note

Keywords: 2',5'-Oligoadenylate Synthetase; Animals; Autoimmune Diseases; Diabetes Mellitus, Experimental; Disease Models, Animal; Dogs; Electrophoresis, Polyacrylamide Gel; Humans; Interferon-alpha; Lymphocytes; Poly I-C; RNA, Double-Stranded; Rats; Rats, Inbred BB; Rats, Inbred Strains; Sheep

ID: 11255724