ENHANCEMENT OF CYTOMEGALOVIRUS-INFECTION AND ACUTE REJECTION AFTER ALLOGENEIC LUNG TRANSPLANTATION IN THE RAT .1. VIRAL INDUCTION EXPRESSION OF ENDOTHELIAL-CELL ADHESION MOLECULES

A possible mechanism of the induction of lung transplant rejection by cytomegalovirus (CMV) infection is the inflammatory upregulation of ad hesion ligand molecules on transplant endothelia by the viral infectio n leading to leukocyte activation. To study this question a rat model of rat cytomegalovirus (RCMV) infection and acute lung transplant reje ction 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 (RT1(1)) rats rec eived either syngenic (n=25) or allogeneic (BN, RT1n; n=38) left later al lung transplants, Postoperatively, CsA 25 mg/kg was given on days 1 -3 and triple drug (CsA, Aza, Pred) immunosuppression was given from d ays 4-10 to induce systemic PCMV infection and acute rejection develop ed from postoperative day (POD) 15-25 in allogeneic transplants, In RC MV-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 an d increased salivary gland PFU titers on days 20 and 25, In the absenc e of rejection infiltration a maximal induction of ICAM-1 adhesion mol ecules was found on lung endothelia in RCMV+ allogeneic animals as com pared with noninfected controls. This induction was found to lesser de gree for VCAM-1 and MHC class II adhesion ligand molecules, This was a ccompanied by a significantly increased CD11a+ and CD49d+ leukocyte in filtration 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 in fluence transplant in inflammation and the long-term course of lung tr ansplant rejection.