title: Association between decreased pulmonary endothelial cell thrombomodulin and local fibrin deposition in pneumonia.
abstract: Thrombomodulin (TM) plays an important role in anticoagulation by forming a complex with thrombin, which subsequently activates protein C. TM is inactivated and downregulated by inflammatory cell mediators. This study examined whether bronchopneumonia is associated with changes in TM immunoreactivity, and whether a decrease in TM is accompanied by evidence of hypercoagulability, i.e. local deposition of fibrin. Double antibody staining for TM and fibrin was performed on lung tissue sections from patients who had died of pneumonia and from patients who had died rapidly, secondary to trauma. Inflammatory changes were assessed histologically and immunohistochemically using antibodies against interleukin-1alpha, tumor necrosis factor-alpha, and myeloperoxidase. Areas with bronchopneumonia exhibited markedly decreased endothelial TM staining of alveolar walls and small vessels. These changes were associated with prominent fibrin immunoreactivity. Some areas exhibited mild to moderate inflammation with little fibrin deposition and variable amounts of TM in adjacent vessels. This study is the first to relate changes of TM immunoreactivity levels to fibrin deposition in a human disease process. These data may have implications for pulmonary pathophysiology in patients with bronchopneumonia.
authors.affiliation: Department of Surgery, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Albertson
authors.forename: K K
authors.initials: KK
authors.lastname: Richter
authors.forename: B J
authors.initials: BJ
authors.lastname: Kudryk
authors.forename: L M
authors.initials: LM
authors.lastname: Fink
authors.forename: M
authors.initials: M
authors.lastname: Hauer-Jensen
mesh_terms: D016207:Cytokines / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D011014:Pneumonia / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D018180:Thrombomodulin / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018180:Thrombomodulin; D005337:Fibrin