Steinhoff G, You X M, Steinmuller C, Bauer D, Lohmann-Matthes M L, Bruggeman C A, Haverich A
The Department of Cardiovascular Surgery, Christian Albrechts University, Kiel, Germany.
Transplantation. 1996 Apr 27;61(8):1250-60. doi: 10.1097/00007890-199604270-00022.
A possible mechanism of the induction of lung transplant rejection by cytomegalovirus (CMV) infection is the inflammatory upregulation of adhesion ligand molecules on transplant endothelia by the viral infection leading to leukocyte activation. To study this question a rat model of rat cytomegalovirus (RCMV) infection and acute lung transplant rejection was established to study: (1) the influence of RCMV infection on the course of rejection, (2) the influence of rejection on the course of RCMV infection, and (3) the influence of RCMV on adhesion molecule expression and leukocyte infiltration. For this Lew (RT1l) rats received either syngenic (n=25) or allogeneic (BN, RT1n; n=38) left lateral lung transplants. Postoperatively, CsA 25mg/kg was given on days 1-3 and triple drug (CsA, Aza, Pred) immunosuppression was given from days 4-10 to induce systemic RCMV infection and acute rejection developed from postoperative day (POD) 15-25 in allogeneic transplants. In RCMV-positive animals the rejection grade was gradually increased at POD 15 and 18. Furthermore, after allogeneic transplantation an enhanced viral infection of the lung transplant as early as POD 11 was found and increased salivary gland PFU titers on days 20 and 25. In the absence of rejection infiltration a maximal induction of ICAM-1 adhesion molecules was found on lung endothelia in RCMV+ allogeneic animals as compared with noninfected controls. This induction was found to lesser degree for VCAM-1 and MHC class II adhesion ligand molecules. This was accompanied by a significantly increased CD11a+ and CD49d+ leukocyte infiltration into the alveolar interstitium on day 11 and 15 in infected transplants. The results show an enhancement of RCMV infection after allogeneic lung transplantation leading to endothelial activation and recruitment of CD11a/CD49d+ leukocytes. This mechanism may strongly influence transplant inflammation and the long-term course of lung transplant rejection.
巨细胞病毒（CMV）感染诱导肺移植排斥反应的一种可能机制是，病毒感染导致移植内皮细胞上的黏附配体分子炎性上调，进而引起白细胞活化。为研究这一问题，建立了大鼠巨细胞病毒（RCMV）感染和急性肺移植排斥反应的大鼠模型，以研究：（1）RCMV感染对排斥反应进程的影响；（2）排斥反应对RCMV感染进程的影响；（3）RCMV对黏附分子表达和白细胞浸润的影响。为此，将Lew（RT1l）大鼠分为两组，分别接受同基因（n = 25）或异基因（BN，RT1n；n = 38）左侧肺移植。术后，第1 - 3天给予环孢素A（CsA）25mg/kg，第4 - 10天给予三联药物（CsA、硫唑嘌呤、泼尼松）免疫抑制，以诱导全身性RCMV感染，异基因移植中急性排斥反应于术后第15 - 25天发生。在RCMV阳性动物中，排斥反应分级在术后第15天和18天逐渐增加。此外，异基因移植后，早在术后第11天就发现肺移植的病毒感染增强，并且在第20天和25天唾液腺空斑形成单位（PFU）滴度增加。在无排斥浸润的情况下，与未感染的对照组相比，RCMV阳性异基因动物的肺内皮细胞上ICAM - 1黏附分子的诱导作用最大。对于VCAM - 1和MHC II类黏附配体分子，这种诱导作用程度较小。这伴随着感染移植在第11天和15天肺泡间质中CD11a +和CD49d +白细胞浸润显著增加。结果表明，异基因肺移植后RCMV感染增强，导致内皮细胞活化和CD11a/CD49d +白细胞募集。这一机制可能强烈影响移植炎症和肺移植排斥反应的长期进程。
