Kuo P C, Alfrey E J, Krieger N R, Abe K Y, Huie P, Sibley R K, Dafoe D C
Department of Surgery, Stanford University Medical Center, CA, USA.
Immunology. 1996 Apr;87(4):647-53. doi: 10.1046/j.1365-2567.1996.468592.x.
Nitric oxide (NO) is a free radical with a diversity of cellular origins and potential functions. Within the realm of solid organ transplantation, NO has been the focus of much attention. Discordant reports have documented both suppression and potentiation of the alloimmune response. In addition to questions regarding its functional role, little is known of the cellular origins of NO in acute rejection of vascularized allografts. To address this question, acute rejection models of rat heterotopic heart and orthotopic liver transplantation were chosen. When compared with naive controls and isografted animals, acute rejection in both heart and liver transplantation was associated with elevated systemic levels of the NO metabolite, nitrite. This was accompanied by increased graft content of iNOS protein as determined by immunoblot analysis of protein extracts. Expression of iNOS mRNA was localized with in situ hybridization. In both heart and liver transplantation, iNOS mRNA was found in the inflammatory infiltrate accompanying acute rejection. In addition, hepatocytes also expressed iNOS mRNA in the rejecting liver allograft. In contrast, cardiac myocytes in the rejecting heart allograft did not stain for iNOS mRNA. These results indicate that organ-specific, differential cellular expression of iNOS occurs in the acutely rejecting allograft. Transcriptional regulation of iNOS may vary among various organs according to the local cellular milieu. In addition, there may be a variable allograft specific response to acute rejection which may modify the associated immunologic biology.
一氧化氮（NO）是一种具有多种细胞来源和潜在功能的自由基。在实体器官移植领域，NO一直是备受关注的焦点。相互矛盾的报道记录了其对同种免疫反应的抑制和增强作用。除了关于其功能作用的问题外，对于血管化同种异体移植物急性排斥反应中NO的细胞来源知之甚少。为了解决这个问题，我们选择了大鼠异位心脏和原位肝脏移植的急性排斥模型。与未处理的对照组和同基因移植动物相比，心脏和肝脏移植中的急性排斥反应均与NO代谢产物亚硝酸盐的全身水平升高有关。通过对蛋白质提取物进行免疫印迹分析确定，这伴随着移植物中诱导型一氧化氮合酶（iNOS）蛋白含量的增加。iNOS mRNA的表达通过原位杂交进行定位。在心脏和肝脏移植中，iNOS mRNA均在急性排斥反应伴随的炎性浸润中被发现。此外，在发生排斥反应的肝脏同种异体移植物中，肝细胞也表达iNOS mRNA。相比之下，发生排斥反应的心脏同种异体移植物中的心肌细胞未检测到iNOS mRNA染色。这些结果表明，在急性排斥的同种异体移植物中存在器官特异性、iNOS的差异性细胞表达。iNOS的转录调控可能因不同器官的局部细胞环境而异。此外，对于急性排斥反应可能存在可变的同种异体移植物特异性反应，这可能会改变相关的免疫生物学特性。
