Effects of intrapulmonary viral tropism and cytokine expression on the histological patterns of cytomegalovirus pneumonia.

Effects of intrapulmonary viral tropism and cytokine expression on the histological patterns of cytomegalovirus pneumonia.
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DOI:
10.1111/j.1440-1827.2012.02849.x
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发表时间:
2012-09
影响因子:
2.2
通讯作者:
Iwashita T
Iwashita T
中科院分区:
医学4区
文献类型:
--
作者:
Arai Y;Tsuchida T;Kosugi I;Kawasaki H;Meguro S;Kinoshita M;Baba S;Maeda M;Shinmura Y;Tsutsui Y;Iwashita T

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肺巨细胞病毒(CMV)感染可导致免疫功能低下患者发生致命性CMV肺炎(CMVp);然而,CMV感染诱导的肺部病变发展的潜在机制在很大程度上仍然未知。我们研究了CMVp模式与肺内病毒嗜性的关系,包括炎性细胞因子和相关分子的表达。CMV抗原和细胞标志物的双重免疫组化显示,上皮嗜性与弥漫性肺泡损伤(DAD)模式(CMVp-DAD)相关,而间质嗜性与主要间质性炎症/纤维化(IIF)(CMVp-IIF)或DAD和IIF的组合(CMVp-复合物)相关。转化生长因子(TGF)-β1的表达与CMV引起的组织损伤有关,CMVp复合体和CMVp-IIF中TGF-β 1的表达高于CMVp-DAD。间质性肺炎中TGF-β1的重要活化因子和粘附分子整合素β6(integrin β 6,ITGB 6)在CMV感染的肺细胞中表达缺失,尤其是CMVp-DAD,而CMVp-复合物和CMVp-IIF中CMV阴性的肺细胞表达过度。CMV感染的肺细胞和间质细胞中均存在弥漫性白细胞介素(IL)-8上调和强表达,仅在CMVp-IIF病例中有显著的间质嗜中性粒细胞浸润。根据CMV的嗜性和TGF-β1、ITGB 6和IL-8的表达,我们认为CMV感染的肺细胞在不同CMVp模式的发展中起重要作用。
Pulmonary cytomegalovirus (CMV) infection causes fatal CMV pneumonia (CMVp) in Immunocompromised patients; however, the mechanisms underlying CMV-Infection-Induced pulmonary lesion development remain largely unknown. We examined the relationship between CMVp patterns and Intrapulmonary viral tropism, Including expression of Inflammatory cytokines and related molecules. Double Immunohistochemistry of CMV antigen and cellular markers showed that epithelial tropism was associated with a diffuse alveolar damage (DAD) pattern (CMVp-DAD) while stromal tropism was associated with a predominantly interstitial inflammation/fibrosis (IIF) (CMVp-IIF) or a combination of DAD and IIF (CMVp-complex). Transforming growth factor (TGF)-β1 expression was relevant to CMV-induced tissue injury, and its expression was higher in CMVp-complex and CMVp-IIF than in CMVp-DAD. Expression of integrin β6 (ITGB6), an adhesion molecule and important activator of TGF-β1 in interstitial pneumonia, was lost in CMV-infected pneumocytes, especially CMVp-DAD, whereas CMV-negative pneumocytes in CMVp-complex and CMVp-IIF showed overexpression. Diffuse interleukin (IL)-8 up-regulation and strong expression were present in both CMV-infected pneumocytes and stromal cells only in CMVp-IIF cases with marked interstitial neutrophilic infiltration. On the basis of viral tropism and the expression of TGF-β1, ITGB6, and IL-8, we conclude that CMV-Infected pulmonary cells play an Important role in the development of diverse CMVp patterns.
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