Stals F S, Steinhoff G, Wagenaar S S, van Breda Vriesman J P, Haverich A, Dormans P, Moeller F, Bruggeman C A
Department of Medical Microbiology, University of Limburg, The Netherlands.
Lab Invest. 1996 Feb;74(2):343-52.
Interstitial lung disease (ILD) after allogeneic bone marrow transplantation (BMTx) is an important clinical problem in terms of diagnosis, therapy, and pathogenesis. Graft-versus-host disease (GvHD) and cytomegalovirus (CMV) infection seem to be major risk factors for ILD, but their role in the pathogenesis is not well established. We previously reported CMV-induced ILD in allogeneic bone marrow recipient rats, which was prevented by antiviral drug treatment. In this paper, we describe the pathology of ILD in allogeneic bone marrow transplant recipient rats and the relation of ILD with CMV infection and GvHD. Brown Norway rats received an allogeneic (Lewis) BMTx and rat CMV infection, after an allogeneic (Lewis) lung transplantation and immunosuppression. CMV infection was recorded by the amount of infectious virus and viral antigens in the lung. ILD was monitored by the presence of diffuse histopathologic changes in the alveolar septal wall. GvHD was scored by the relative splenic weights and the presence of perivascular infiltrates in the lung. Cells expressing CMV antigens were more numerous in the alveolar septa of the allogeneic recipient lungs than in the syngeneic donor lungs (p < 0.05). The high viral load in the recipient lung of allogeneic BMTx recipient rats was accompanied by diffuse ILD, marked by extensive microvascular damage and congestion of the alveolar septa. ILD was observed neither in the syngeneic donor lung nor in both lungs of mock-infected animals. GvHD was not observed in rat-CMV-infected or in mock-infected animals. Our results indicate that CMV induces microvascular damage, resulting in ILD. This process is independent of GvHD.
异基因骨髓移植（BMTx）后的间质性肺疾病（ILD）在诊断、治疗和发病机制方面是一个重要的临床问题。移植物抗宿主病（GvHD）和巨细胞病毒（CMV）感染似乎是ILD的主要危险因素，但其在发病机制中的作用尚未完全明确。我们之前报道了异基因骨髓移植受体大鼠中CMV诱导的ILD，抗病毒药物治疗可预防这种情况。在本文中，我们描述了异基因骨髓移植受体大鼠中ILD的病理学以及ILD与CMV感染和GvHD的关系。棕色挪威大鼠在接受异基因（Lewis）肺移植和免疫抑制后，接受了异基因（Lewis）BMTx和大鼠CMV感染。通过肺中感染性病毒和病毒抗原的量来记录CMV感染。通过肺泡间隔壁中弥漫性组织病理学变化的存在来监测ILD。通过相对脾脏重量和肺血管周围浸润的存在对GvHD进行评分。与同基因供体肺相比，异基因受体肺的肺泡间隔中表达CMV抗原的细胞更多（p < 0.05）。异基因BMTx受体大鼠受体肺中的高病毒载量伴随着弥漫性ILD，其特征为广泛的微血管损伤和肺泡间隔充血。在同基因供体肺或假感染动物的双肺中均未观察到ILD。在大鼠CMV感染或假感染动物中未观察到GvHD。我们的结果表明，CMV诱导微血管损伤，导致ILD。这个过程独立于GvHD。
