title: Effects of intrapulmonary viral tropism and cytokine expression on the histological patterns of cytomegalovirus pneumonia.
abstract: 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.
authors.affiliation: Department of Pathology, Hamamatsu University School of Medicine, Hamamtsu, Japan. y-arai@hama-med.ac.jp
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Arai
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuchida
authors.forename: Isao
authors.initials: I
authors.lastname: Kosugi
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Shiori
authors.initials: S
authors.lastname: Meguro
authors.forename: Mana
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Baba
authors.forename: Matsuyoshi
authors.initials: M
authors.lastname: Maeda
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Shinmura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tsutsui
authors.forename: Toshihide
authors.initials: T
authors.lastname: Iwashita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism* / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011024:Pneumonia, Viral / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D056189:Viral Tropism / Q000502:physiology*
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D039641:Integrin beta Chains; D016209:Interleukin-8; D053773:Transforming Growth Factor beta1; C072170:integrin beta6