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Updated: May 19, 2026
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Published on: May 14, 2013
Endothelial nitric oxide synthase inhibits the development of autoimmune-mediated vasculitis in mice
Trenton R Schoeb1, Tambi Jarmi, M John Hicks
1University of Alabama at Birmingham, 720 South 20th Street, Birmingham, AL 35294, USA.
Objective:
Many different genes or mediators have been implicated in promoting the development of vasculitis, although little is known regarding the mechanisms that normally act to suppress lesion formation. Endothelial nitric oxide synthase (eNOS) has been shown to inhibit vascular inflammation in many different model systems, but its roles in the pathogenesis of vasculitis have not been elucidated. This study was undertaken to determine the functions of eNOS in the initiation and progression of vasculitic lesion formation.
Methods:
MRL/MpJ-Fas(lpr) mice lacking the gene for eNOS (Nos3(-/-) ) were generated and comprehensively evaluated and compared to controls with regard to the development of autoimmune disease, including vasculitic lesion formation and glomerulonephritis.
Results:
Nos3(-/-) MRL/MpJ-Fas(lpr) mice exhibited accelerated onset and increased incidence of renal vasculitis compared to Nos3(+/+) controls. In contrast, no significant differences in severity of glomerulonephritis were observed between groups. Vasculitis was also observed in other organs of eNOS-deficient mice, including in the lungs of several of these animals. Ultrastructural analyses of renal lesions revealed the presence of electron-dense deposits in affected arteries, and IgG, IgA, and C3 deposition was observed in some vessels in the kidneys of Nos3(-/-) mice. In addition, Nos3(-/-) MRL/MpJ-Fas(lp) mice showed increased levels of circulating IgG-IgA immune complexes at 20 weeks of age, compared to Nos3(+/+) MRL/MpJ-Fas(lpr) and Nos3(-/-) C57BL/6 mice.
Conclusion:
These findings strongly indicate that eNOS serves as a negative regulator of vasculitis in MRL/MpJ-Fas(lpr) mice and further suggest that NO produced by this enzyme may be critical for inhibiting lesion formation and vascular damage in human vasculitic diseases.
Insights
Endothelial nitric oxide synthase (eNOS) suppresses vasculitis development. Mice lacking eNOS showed accelerated renal vasculitis, indicating eNOS is crucial for inhibiting vascular inflammation and damage in autoimmune diseases.
Area of Science:
- Immunology
- Vascular Biology
- Pathogenesis of Autoimmune Diseases
Background:
- Vasculitis pathogenesis involves various genes, but suppressive mechanisms are unclear.
- Endothelial nitric oxide synthase (eNOS) inhibits vascular inflammation in models.
- The role of eNOS in vasculitis pathogenesis requires elucidation.
Purpose of the Study:
- To determine the function of eNOS in vasculitic lesion initiation and progression.
- To investigate eNOS's role in suppressing autoimmune disease development.
Main Methods:
- Generated MRL/MpJ-Fas(lpr) mice lacking eNOS (Nos3(-/-)).
- Compared vasculitic lesion formation and glomerulonephritis in Nos3(-/-) mice versus controls.
- Utilized ultrastructural analysis and immunological assays to evaluate kidney lesions.
Main Results:
- Nos3(-/-) mice exhibited accelerated onset and increased incidence of renal vasculitis.
- No significant difference in glomerulonephritis severity was observed.
- Immune complex deposition (IgG, IgA, C3) and elevated circulating IgG-IgA immune complexes were noted in Nos3(-/-) mice.
Conclusions:
- eNOS acts as a negative regulator of vasculitis in MRL/MpJ-Fas(lpr) mice.
- Nitric oxide (NO) produced by eNOS is critical for inhibiting vasculitic lesion formation.
- Findings suggest eNOS's protective role in human vasculitic diseases.
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