Raised protein levels and altered cellular expression of factor VII activating protease (FSAP) in the lungs of patients with acute respiratory distress syndrome (ARDS).
BACKGROUND
The acute respiratory distress syndrome (ARDS) is characterised by inflammation of the lung parenchyma and changes in alveolar haemostasis with extravascular fibrin deposition. Factor VII activating protease (FSAP) is a recently described serine protease in plasma and tissues known to be involved in haemostasis, cell proliferation and migration.


METHODS
The level of FSAP protein expression was examined by western blotting/ELISA/immunohistochemistry and its activity was investigated by coagulation/fibrinolysis assays in plasma, bronchoalveolar lavage (BAL) fluid and lung tissue of mechanically ventilated patients with early ARDS and compared with patients with cardiogenic pulmonary oedema and healthy controls. Cell culture experiments were performed to assess the influence of different inflammatory stimuli on FSAP expression by various cell populations of the lung.


RESULTS
FSAP protein level and activity were markedly increased in the plasma and BAL fluid of patients with ARDS with a significant contribution to the increased alveolar procoagulant activity. Immunoreactivity for FSAP was observed in alveolar macrophages, bronchial epithelial and endothelial cells of lungs of patients with ARDS, while in controls the immunoreactivity for FSAP was restricted to alveolar macrophages. Only a low basal level of FSAP expression was detected in these cell populations. However, FSAP-specific mRNA expression was induced by lipopolysaccharide and interleukin-8 in human lung microvascular endothelial cells and in bronchial epithelial cells. FSAP was also found to be taken up by alveolar macrophages and degraded within the lysosomal compartment.


CONCLUSIONS
Increased levels of FSAP and an altered cellular expression pattern are found in the lungs of patients with ARDS. This may represent a novel pathological mechanism which contributes to pulmonary extravascular fibrin deposition and may also modulate inflammation in the acutely injured lung via haemostasis-independent cellular activities of FSAP.
Wygrecka
Malgorzata
M
Department of Biochemistry, Faculty of Medicine, University of Giessen Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany. malgorzata.wygrecka@innere.med.uni-giessen.de
Markart
Philipp
P
Fink
Ludger
L
Guenther
Andreas
A
Preissner
Klaus T
KT
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology*; D016676:Macrophages, Alveolar / Q000201:enzymology; D008833:Microcirculation; D012333:RNA, Messenger / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000378:metabolism*
D012333:RNA, Messenger; C433550:HABP2 protein, human; D012697:Serine Endopeptidases