Mice deficient in inducible nitric oxide synthase are susceptible to experimental autoimmune uveoretinitis.
OBJECTIVE
Nitric oxide (NO) is an important mediator of inflammatory tissue damage. The present study addresses the question whether inducible nitric oxide synthase (iNOS), and consequently the ability to upregulate NO, is required to effect the pathogenesis of experimental autoimmune uveoretinitis (EAU) in mice.


METHODS
Mice with a homologous disruption of the iNOS gene (iNOS KO) were evaluated for their ability to develop EAU and associated cellular responses after immunization with the interphotoreceptor retinoid-binding protein. EAU was determined by histopathology 21 days after uveitogenic immunization, and antigen-specific cellular responses were assessed by delayed type hypersensitivity and lymphocyte proliferation.


RESULTS
iNOS knockout (iNOS KO) mice developed EAU with scores similar to wild-type mice and exhibited good cellular responses to the immunizing antigen.


CONCLUSIONS
A functional iNOS gene is not necessary for EAU pathogenesis. Therefore, upregulation of NO is not required to mediate autoimmune tissue damage in the eye.
Silver
P B
PB
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Tarrant
T K
TK
Chan
C C
CC
Wiggert
B
B
Caspi
R R
RR
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004198:Disease Susceptibility / Q000503:physiopathology; D005136:Eye Proteins; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012016:Reference Values; D012173:Retinitis / Q000209:etiology* / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology / Q000494:pharmacology; D014605:Uveitis / Q000209:etiology* / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial; C496317:Nos2 protein, mouse