[2173] Effect of eNOS Deficiency on Glomerulonephritis in Murine Lupus-Like Model

John Hicks, Trenton Schoeb, Daniel Bullard. Texas Children's Hospital & Baylor College of Medicine, Houston, TX; University of Alabama - Birmingham, Birmingham, AL

Background: Endothelial nitric oxide synthase (eNOS) is a constitutively active enzyme primarily expressed in endothelial cells and plays important roles in regulating vasodilatation, inhibiting smooth muscle proliferation and platelet aggregation, modulating leukocyte/endothelium adhesion events, and controlling key vascular functions. To examine the possible involvement of eNOS in the context of vasculitis and glomerulonephritis, Nos3 (eNOS) mutation on background of MRL/MpJ-Faslpr mice (murine lupus-like model) was generated.
Design: MRL/MpJ-Faslpr mice deficient in eNOS were generated by sequentially backcrossing Nos3 mutation (8 generations) onto MRL/MpJ-Faslpr strain, and homozygotes (Nos3-/-) and heterozygotes (Nos3+/-) were generated by intercrossing. Kidney tissues from eNOS+/+, eNOS+/-, and eNOS-/- genotyped MRL/MpJ-Faslpr mice were obtained for routine microscopic (H&E, PAS, trichrome) and electron microscopic examination. 5 mice in each of the 3 genotype groups were sacrificed at weeks 20 and 22.
Results: Wild type eNOS+/+ kidneys showed a moderate increase in mesangial cells and matrix without segmental lesions or crescents. There were readily identifiable intermediate to large electron dense deposits within the mesangium, paramesangium and basement membranes with foot process effacement. There were no vasculitic features and no deposits with the vessels or tubules. Heterozygote eNOS+/- kidneys showed a mild increase in mesangial cells and matrix with mesangial and paramesangial electron dense deposits. Frequency and size of deposits were decreased compared with eNOS+/+. Basement membrane deposits were not identified. There was no vasculitis or deposits with the vessels or tubules. Occasional aggregates of lymphocytes and plasma cells were present. Null eNOS-/- kidneys had mild mesangial matrix and cell increase. Mesangium and paramesangium contained fine small electron dense deposits. Rare small subendothelial deposits were seen. There were prominent perivascular aggregates of lymphocytes and plasma cells with electron dense deposits in perivascular adventitia.
Conclusions: eNOS deficiency in a murine lupus model tended to decrease mesangial, paramesangial and membranous deposits with its greatest effect in the null group (eNOS-/-). However, perivascular lymphoplasmacytic infiltrates with adventitial deposits occurred with the null eNOS-/- group. A partial loss of eNOS function may be beneficial in modulation of glomerulonephritis while avoiding vasculitis associated with complete loss of eNOS function.
Category: Ultrastructural

Wednesday, March 21, 2012 9:30 AM

Poster Session V # 314, Wednesday Morning

 

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