Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome.

Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome.

MedLine Citation:	PMID: 2314423 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	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.

Authors:	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
Affiliation:	Department of Medicine, Brigham and Women's Hospital, Boston, MA.
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MeSH Terms
Descriptor/Qualifier:	Adult Antigens / analysis Bronchoalveolar Lavage Fluid / enzymology* Female Fibrin / metabolism Fibronectins / metabolism Humans Lung Diseases / enzymology Male Middle Aged Respiratory Distress Syndrome, Adult / enzymology, etiology Urokinase-Type Plasminogen Activator / antagonists & inhibitors, immunology, metabolism alpha-2-Antiplasmin / metabolism
Grant Support
ID/Acronym/Agency:	HL 23591/HL/NHLBI NIH HHS; HL 36563/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:	0/Antigens; 0/Fibronectins; 0/alpha-2-Antiplasmin; 9001-31-4/Fibrin; EC 3.4.21.73/Urokinase-Type Plasminogen Activator
Comments/Corrections
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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