Inducible nitric oxide synthase inhibition of Weibel-Palade body release in cardiac transplant rejection

Background-Inducible nitric oxide synthase (iNOS, or NOS2) reduces the seve rity of accelerated graft arteriosclerosis (AGA) in transplanted organs, al though the precise mechanism is unclear. Methods and Results-We transplanted wild-type murine hearts into either wil d-type or NOS2-null recipient mice; we then measured cardiac allograft surv ival and analyzed tissue sections by immunohistochemistry. We have confirme d that NOS2 increases cardiac allograft survival. We now show that there is less inflammation of cardiac allografts in wild-type hosts than in NOS2-nu ll hosts. Furthermore, staining for von Willebrand factor reveals that the presence of NOS2 is correlated with the presence of Weibel-Palade bodies in side endothelial cells, whereas the absence of NOS2 is correlated with the release of Weibel-Palade bodies. Conclusions-Weibel-Palade bodies contain mediators that promote thrombosis and inflammation. Therefore, nitric oxide (NO) may stabilize the vessel wal l and prevent endothelial activation in part by inhibiting the release of t he contents of Weibel-Palade bodies. Prevention of Weibel-Palade body relea se might be a mechanism by which NO protects the vessel wall from inflammat ory disorders such as atherosclerosis or graft arteriosclerosis.