Development of lyme arthritis in mice deficient in inducible nitric oxide synthase.
Nitric oxide (NO) is a powerful antimicrobial agent and an important regulatory molecule of the innate immune response. To determine if NO has a role in experimental Lyme disease, arthritis-resistant DBA/2J and arthritis-susceptible C3H/HeJ mice were bred to be genetically deficient for inducible NO synthase (iNOS). Following footpad injection of Borrelia burgdorferi, arthritis was similar between iNOS-deficient and control animals regardless of their genetic background. Histologic examination and arthritis severity scores of ankles revealed no differences in arthritis development between iNOS-deficient and control animals. Despite being deficient in a key antimicrobial agent, iNOS-deficient mice had tissue levels of B. burgdorferi similar to those in control mice. Thus, NO does not have a critical role in susceptibility to Lyme arthritis through tissue damage via an overexuberant inflammatory response, nor is it required in resistance through the clearance of spirochetes from tissues.
Brown
C R
CR
Department of Medicine, University of Chicago, Chicago, IL 60637. cbrown@midway.uchicago.edu
Reiner
S L
SL
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000302:isolation & purification; D001170:Arthritis, Infectious / Q000276:immunology* / Q000473:pathology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000302:isolation & purification; D001428:Bacterial Vaccines; D004198:Disease Susceptibility; D007113:Immunity, Innate; D015847:Interleukin-4 / Q000235:genetics; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D019001:Nitric Oxide Synthase / Q000172:deficiency*; D052247:Nitric Oxide Synthase Type II; D013643:Tarsus, Animal / Q000473:pathology
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; C072045:OspA protein; D015847:Interleukin-4; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse