Document Detail

Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome.
MedLine Citation:
PMID:  2314423     Owner:  NLM     Status:  MEDLINE    
Abundant deposition of bronchoalveolar fibrin and fibronectin occurs during the exudative phase of the adult respiratory distress syndrome (ARDS), promoting hyaline-membrane formation and subsequent alveolar fibrosis. To explore the mechanisms that account for the persistence of bronchoalveolar fibrin and fibronectin, we compared the activity of urokinase, which is necessary for plasminogen activation and fibrin degradation, in cell-free bronchoalveolar-lavage fluid from 8 patients with ARDS, 9 patients with acute pulmonary diseases other than ARDS, and 10 normal subjects. The mean level of urokinase activity in the lavage fluid from the patients with ARDS was 0.003 IU per milliliter of fluid (range, 0 to 0.008), which was significantly lower (P = 0.001) than the level in the fluid from either the patients with pulmonary diseases other than ARDS (0.118 IU per milliliter [range, 0.032 to 0.295]) or the normal subjects (0.129 IU per milliliter [range, 0.045 to 0.198]). The lavage fluid from all the patients with ARDS also had antiplasmin activity, which would promote the persistence of fibrin. A true decrease in urokinase activity was confirmed by the failure of the lavage fluid from the patients with ARDS to convert [125I]plasminogen to plasmin. Despite the low urokinase activity, immunochemical assays revealed normal levels of urokinase antigen in the fluid from the patients with ARDS, suggesting the presence of urokinase inhibitors. Inhibitors were demonstrated directly by a fibrin gel-underlay assay that detects complexes of urokinase with inhibitors. Plasminogen-activator inhibitor type 1 was the principal inhibitor identified. We conclude that increased antifibrinolytic activity due to both urokinase inhibitors and antiplasmins in the bronchoalveolar compartment of patients with ARDS contributes to the formation and persistence of hyaline membranes, a key component of alveolar histopathology in ARDS.
P Bertozzi; B Astedt; L Zenzius; K Lynch; F LeMaire; W Zapol; H A Chapman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The New England journal of medicine     Volume:  322     ISSN:  0028-4793     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  1990 Mar 
Date Detail:
Created Date:  1990-04-19     Completed Date:  1990-04-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  890-7     Citation Subset:  AIM; IM    
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
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MeSH Terms
Antigens / analysis
Bronchoalveolar Lavage Fluid / enzymology*
Fibrin / metabolism
Fibronectins / metabolism
Lung Diseases / enzymology
Middle Aged
Respiratory Distress Syndrome, Adult / enzymology*,  etiology
Urokinase-Type Plasminogen Activator / antagonists & inhibitors,  immunology,  metabolism*
alpha-2-Antiplasmin / metabolism
Grant Support
Reg. No./Substance:
0/Antigens; 0/Fibronectins; 0/alpha-2-Antiplasmin; 9001-31-4/Fibrin; EC Plasminogen Activator
Comment In:
N Engl J Med. 1990 Mar 29;322(13):929-31   [PMID:  2314427 ]
N Engl J Med. 1990 Aug 9;323(6):422   [PMID:  2242136 ]

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