Up-regulation of inducible nitric oxide synthase mRNA in dogs experimentally infected with Borrelia burgdorferi

The up-regulation of the inducible nitric oxide synthase (iNOS) mRNA was de termined by RT-PCR in 25 tissues each from 22 specific pathogen-free (SPF) dogs experimentally infected with Borrelia burgdorferi by tick exposure and from five uninfected control dogs. Using primers specific for a homologous region of the human and canine iNOS sequence, and canine macrophage mRNA, we isolated and partially sequenced canine iNOS. A sequence of 1775 bases w as obtained and primers specific for canine iNOS mRNA constructed to invest igate the expression of iNOS in dog tissues in response to infection with B . burgdorferi. In 12 out of 22 dogs infected with B. burgdorferi, acute lam eness occurred within 55-82 days after infection whereas the other 10 dogs showed no or only mild clinical signs despite persistent infection up to Da y 175. The numbers of iNOS mRNA-positive tissues in dogs with acute lamenes s were significantly higher than in dogs without lameness, while uninfected dogs showed only negligible iNOS expression. Dogs with acute lameness also had higher numbers of borrelia-positive tissues as well as higher scores i n histopathological evaluations than infected dogs without lameness. Our re sults show that the expression of iNOS mRNA is related to the number of B. burgdorferi-positive tissues and the severity of inflammation as assessed b y histopathology, These results implicate an up-regulation of the iNOS mRNA as part of the host's immune response to borrelia infection and a possible role for NO in the pathogenesis of canine Lyme arthritis. (C) 1999 Elsevie r Science B.V. All rights reserved.