title: Thrombin-activatable fibrinolysis inhibitor and protein C inhibitor in interstitial lung disease.
abstract: Intraalveolar activation of the coagulation system due to reduced fibrinolytic function plays a critical role in the pathogenesis of interstitial lung disease. Recently, a new potent inhibitor of fibrinolysis, thrombin-activatable fibrinolysis inhibitor, has been isolated and characterized from human plasma. This study evaluated the levels of thrombin-activatable fibrinolysis inhibitor and protein C inhibitor, another suppressor of fibrinolysis, in the bronchoalveolar lavage fluid from patients with interstitial lung disease. There were 82 patients with interstitial lung disease and 8 normal subjects. The bronchoalveolar lavage fluid levels of thrombin-activatable fibrinolysis inhibitor and protein C inhibitor were significantly higher in all patients with interstitial lung disease than in normal subjects. Both inhibitors of fibrinolysis were significantly and inversely correlated with fibrinolytic activity in all patients. The levels of thrombin-activatable fibrinolysis inhibitor were significantly correlated with those of protein C inhibitor, thrombin-antithrombin complex, and monocyte chemoattractant protein-1. Reverse transcriptase-polymerase chain reaction showed that alveolar macrophages isolated from patients with interstitial lung disease as well as immortalized lung epithelial cell lines express thrombin-activatable fibrinolysis inhibitor antigen. Overall, these findings suggest that thrombin-activatable fibrinolysis inhibitor and protein C inhibitor may play important roles in the mechanism of intraalveolar hypofibrinolysis associated with interstitial lung diseases.
authors.affiliation: Respiratory Division, Third Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu City, Mie 514-8507, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Esteban Cesar
authors.initials: EC
authors.lastname: Gabazza
authors.forename: Osamu
authors.initials: O
authors.lastname: Hataji
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Yuda
authors.forename: Corina Nayade
authors.initials: CN
authors.lastname: D'Alessandro-Gabazza
authors.forename: Mariko
authors.initials: M
authors.lastname: Nakano
authors.forename: Omar Enrique
authors.initials: OE
authors.lastname: Franco
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Adachi
authors.forename: Osamu
authors.initials: O
authors.lastname: Taguchi
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000473:pathology; D000990:Antithrombin III / Q000032:analysis; D001706:Biopsy; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D025901:Carboxypeptidase B2 / Q000032:analysis* / Q000276:immunology; D016022:Case-Control Studies; D002460:Cell Line; D018932:Chemokine CCL2 / Q000032:analysis; D003095:Collagen Diseases / Q000473:pathology; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D008297:Male; D010447:Peptide Hydrolases / Q000032:analysis; D010958:Plasminogen / Q000032:analysis; D018046:Protein C Inhibitor / Q000032:analysis*; D011657:Pulmonary Eosinophilia / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017565:Sarcoidosis, Pulmonary / Q000473:pathology
chemical_list: D018932:Chemokine CCL2; D018046:Protein C Inhibitor; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010958:Plasminogen; D010447:Peptide Hydrolases; D025901:Carboxypeptidase B2