Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Nitric oxide (NO) is a small molecule derived from L-arginine that governs a myriad of physiologic processes including the antimicrobial and tumoricidal responses. Although NO is typically recognized as pro-inflammatory, it is also imperative in the inhibition of lymphocyte proliferation, down regulation of MHC II, and apoptosis of T cells. Here, we examined the role of NO in mediating peripheral tolerance using a model of spontaneous kidney allograft acceptance. DBA/2J kidneys were transplanted into wild-type C57BL/6 and C57BL/6J NOS2 knock-out (KO) mice, and renal function was monitored by blood urea nitrogen. FoxP3+ Tregs were quantified in paraffin-fixed sections on days 7 and 67. Tolerant renal allografts in wild-type C57BL/6 recipients were characterized by widespread nitrosylation, and the presence of inducible nitric oxide synthase (iNOS) positive cells organized around Treg rich organized lymphoid structures (TOLS) (data not shown). Ablation of recipient iNOS activity significantly reduced allograft survival from 100% to 40% (Figure 1A). In NOS2 KO recipients, there was a four-fold decrease in FoxP3+ Tregs in TOLS on days 7 and 67 compared to wild-type recipients (Figure 1B). These data suggest that recipient-derived NO plays an important role in inducing tolerance perhaps by the de novo induction of Tregs.
CITATION INFORMATION: Aljabban I., Jiang B., Yang C., O'Shea T., Ndishabandi D., White R., Russell P., Colvin R., Madsen J., Alessandrini A. NOS2 Deficiency Limits Long Term Survival of Murine Kidney Allografts Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Aljabban I, Jiang B, Yang C, O'Shea T, Ndishabandi D, White R, Russell P, Colvin R, Madsen J, Alessandrini A. NOS2 Deficiency Limits Long Term Survival of Murine Kidney Allografts [abstract]. https://atcmeetingabstracts.com/abstract/nos2-deficiency-limits-long-term-survival-of-murine-kidney-allografts/. Accessed October 13, 2019.
« Back to 2018 American Transplant Congress