Rat cytomegalovirus and Listeria monocytogenes infection enhance chronic rejection after allogenic rat lung transplantation

Abstract

The role of infection in the pathomechanism of obliterative bronchiolitis (OB) after human lung transplantation is controversial. In a rat lung transplantation model, we analyzed the effect of viral [rat cytomegalovirus (RCMV)] and bacterial infection [Listeria monocytogenes (LM)] on the development of chronic allograft rejection. Fisher rats underwent single left lung transplantation with allografts from Lewis rats. Postoperatively, animals were infected with either RCMV or LM, or served as noninfected controls. Animals were killed on day 120 and both lungs were evaluated histopathologically for chronic airway and chronic vascular rejection. Infection with RCMV produced a significant increase in the incidence of chronic airway rejection (66.7% vs. 20%), compared with noninfected long-term surviving animals. In rats with bacterial infection (LM) a similar increase of chronic airway changes as in viral infection (50% vs. 20%) was observed. Chronic rejection of allografts infected with either RCMV or LM was associated with significantly enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on the endothelium. More infiltrating leukocytes (CD18, CD11a, CD44) and ED1-positive macrophages were found in allografts of infected animals. In this experimental model of chronic airway rejection in long-term surviving rats, not only viral but also bacterial infection resulted in enhanced development of chronic airway and vascular rejection. These results support our hypothesis that infectious complications have a substantial influence on the development of OB in human lung allografts.