Avihingsanon Yingyos, Ma Naili, Csizmadia Eva, Wang Candace, Pavlakis Martha, Giraldo Mauricio, Strom Terry B, Soares Miguel P, Ferran Christiane
Division of Immunology, Department of Medicine, Immunobiology Research Center, Harvard Medical School, Boston, MA 02215, USA.
Transplantation. 2002 Apr 15;73(7):1079-85. doi: 10.1097/00007890-200204150-00011.
Long-term survival of a graft requires inhibition of host immune effectors, but protective responses emanating from the graft might be equally important. Expression of the "protective" genes A20, heme-oxygenase-1 (HO-1), and Bcl-xL in rodent allo and xenografts correlates with long-term survival. Little is known of the pattern of expression of such protective genes and the implication thereof in clinical transplantation.
We analyzed, by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry, expression of A20, HO-1, and Bcl-xL in 31 renal allograft biopsies from patients with suspected rejection.
A20 is not expressed in nonrejecting (NR) grafts. Its expression is increased in grafts undergoing acute and chronic rejection (AR and CR) but is weaker in CR. HO-1 is not expressed in NR grafts; it is up-regulated in AR but not CR. Bcl-xL is detected in all biopsies with decreased levels in CR. Expression of A20, HO-1, and Bcl-xL localizes mainly to endothelial, smooth muscle, and infiltrating mononuclear cells.
This data demonstrate that A20 and HO-1 are up-regulated in response to immune injury inferred by AR. Given the antiapoptotic and antiinflammatory functions of these genes, we hypothesize that their expression survives to limit graft injury by maintaining cell viability and controlling inflammation. Their reduced expression in CR as compared with AR represents either inadequate response to injury or a sequelae of prior injury that jeopardizes further tissue response to immune attack.
移植物的长期存活需要抑制宿主免疫效应细胞，但移植物产生的保护性反应可能同样重要。啮齿动物同种异体和异种移植物中“保护性”基因A20、血红素加氧酶-1（HO-1）和Bcl-xL的表达与长期存活相关。对于此类保护性基因的表达模式及其在临床移植中的意义知之甚少。
我们通过定量逆转录聚合酶链反应（RT-PCR）和免疫组织化学分析了31例疑似排斥反应患者的肾移植活检组织中A20、HO-1和Bcl-xL的表达。
A20在未发生排斥反应（NR）的移植物中不表达。其在发生急性和慢性排斥反应（AR和CR）的移植物中表达增加，但在CR中较弱。HO-1在NR移植物中不表达；它在AR中上调，但在CR中未上调。Bcl-xL在所有活检组织中均有检测到，在CR中水平降低。A20、HO-1和Bcl-xL的表达主要定位于内皮细胞、平滑肌细胞和浸润的单核细胞。
这些数据表明，A20和HO-1在AR推断的免疫损伤反应中上调。鉴于这些基因的抗凋亡和抗炎功能，我们推测它们的表达通过维持细胞活力和控制炎症来限制移植物损伤。与AR相比，它们在CR中的表达降低，要么代表对损伤的反应不足，要么代表先前损伤的后遗症，这会危及组织对免疫攻击的进一步反应。
