Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin

Rudolf Lucas, H. Roger Lijnen, Anthony F. Suffredini, Michael S. Pepper, Kenneth P. Steinberg, Thomas R. Martin, Jérôme Pugin

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Acute respiratory distress syndrome (ARDS) is characterized by a disruption of the alveolar-capillary barrier, due to both an epithelial and an endothelial dysfunction. Whereas epithelial apoptosis seems to be mainly mediated by Fas ligand, the mediators of endothelial damage remain to be identified. Angiostatin, a powerful inhibitor of angiogenesis in vivo, also specifically induces apoptosis in endothelial cells. The concentration of various enzymes that cleave angiostatin from plasminogen was reported to be significantly increased in bronchalveolar lavage (BAL) fluids from patients with ARDS. Therefore, in this study, we investigated whether angiostatin was generated during the pulmonary inflammatory response of both healthy subjects challenged with endobronchial endotoxin and in patients with ARDS. We found significantly elevated angiostatin levels in BAL fluids from patients at risk for and with early ARDS (up to 0.022% and 0.018% of total protein, respectively), as well as in BAL fluids from volunteers treated with endotoxin (up to 1.17% of total protein), as compared to BAL fluids from control patients (<0.005% of total protein). These data suggest that angiostatin may contribute to the endothelial damage observed in ARDS, probably via an increased permeability of the alveolar capillary barrier, allowing for an intra-alveolar processing of its precursor plasminogen.

Original languageEnglish (US)
Pages (from-to)966-971
Number of pages6
JournalThrombosis and Haemostasis
Volume87
Issue number6
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Angiostatins
Adult Respiratory Distress Syndrome
Bronchoalveolar Lavage Fluid
Endotoxins
Therapeutic Irrigation
Volunteers
Lung
Plasminogen
Apoptosis
Proteins
Fas Ligand Protein
Angiogenesis Inhibitors
Capillary Permeability
Healthy Volunteers
Endothelial Cells
Enzymes

Keywords

  • Adult respiratory distress syndrome
  • Angiostatin
  • Endothelium
  • Lipopolysaccharide

ASJC Scopus subject areas

  • Hematology

Cite this

Lucas, R., Lijnen, H. R., Suffredini, A. F., Pepper, M. S., Steinberg, K. P., Martin, T. R., & Pugin, J. (2002). Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin. Thrombosis and Haemostasis, 87(6), 966-971.

Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin. / Lucas, Rudolf; Lijnen, H. Roger; Suffredini, Anthony F.; Pepper, Michael S.; Steinberg, Kenneth P.; Martin, Thomas R.; Pugin, Jérôme.

In: Thrombosis and Haemostasis, Vol. 87, No. 6, 01.01.2002, p. 966-971.

Research output: Contribution to journalArticle

Lucas, R, Lijnen, HR, Suffredini, AF, Pepper, MS, Steinberg, KP, Martin, TR & Pugin, J 2002, 'Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin', Thrombosis and Haemostasis, vol. 87, no. 6, pp. 966-971.
Lucas, Rudolf ; Lijnen, H. Roger ; Suffredini, Anthony F. ; Pepper, Michael S. ; Steinberg, Kenneth P. ; Martin, Thomas R. ; Pugin, Jérôme. / Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin. In: Thrombosis and Haemostasis. 2002 ; Vol. 87, No. 6. pp. 966-971.
@article{24dd144a8c4645c9a405cb794dd245c4,
title = "Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin",
abstract = "Acute respiratory distress syndrome (ARDS) is characterized by a disruption of the alveolar-capillary barrier, due to both an epithelial and an endothelial dysfunction. Whereas epithelial apoptosis seems to be mainly mediated by Fas ligand, the mediators of endothelial damage remain to be identified. Angiostatin, a powerful inhibitor of angiogenesis in vivo, also specifically induces apoptosis in endothelial cells. The concentration of various enzymes that cleave angiostatin from plasminogen was reported to be significantly increased in bronchalveolar lavage (BAL) fluids from patients with ARDS. Therefore, in this study, we investigated whether angiostatin was generated during the pulmonary inflammatory response of both healthy subjects challenged with endobronchial endotoxin and in patients with ARDS. We found significantly elevated angiostatin levels in BAL fluids from patients at risk for and with early ARDS (up to 0.022{\%} and 0.018{\%} of total protein, respectively), as well as in BAL fluids from volunteers treated with endotoxin (up to 1.17{\%} of total protein), as compared to BAL fluids from control patients (<0.005{\%} of total protein). These data suggest that angiostatin may contribute to the endothelial damage observed in ARDS, probably via an increased permeability of the alveolar capillary barrier, allowing for an intra-alveolar processing of its precursor plasminogen.",
keywords = "Adult respiratory distress syndrome, Angiostatin, Endothelium, Lipopolysaccharide",
author = "Rudolf Lucas and Lijnen, {H. Roger} and Suffredini, {Anthony F.} and Pepper, {Michael S.} and Steinberg, {Kenneth P.} and Martin, {Thomas R.} and J{\'e}r{\^o}me Pugin",
year = "2002",
month = "1",
day = "1",
language = "English (US)",
volume = "87",
pages = "966--971",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "6",

}

TY - JOUR

T1 - Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin

AU - Lucas, Rudolf

AU - Lijnen, H. Roger

AU - Suffredini, Anthony F.

AU - Pepper, Michael S.

AU - Steinberg, Kenneth P.

AU - Martin, Thomas R.

AU - Pugin, Jérôme

PY - 2002/1/1

Y1 - 2002/1/1

N2 - Acute respiratory distress syndrome (ARDS) is characterized by a disruption of the alveolar-capillary barrier, due to both an epithelial and an endothelial dysfunction. Whereas epithelial apoptosis seems to be mainly mediated by Fas ligand, the mediators of endothelial damage remain to be identified. Angiostatin, a powerful inhibitor of angiogenesis in vivo, also specifically induces apoptosis in endothelial cells. The concentration of various enzymes that cleave angiostatin from plasminogen was reported to be significantly increased in bronchalveolar lavage (BAL) fluids from patients with ARDS. Therefore, in this study, we investigated whether angiostatin was generated during the pulmonary inflammatory response of both healthy subjects challenged with endobronchial endotoxin and in patients with ARDS. We found significantly elevated angiostatin levels in BAL fluids from patients at risk for and with early ARDS (up to 0.022% and 0.018% of total protein, respectively), as well as in BAL fluids from volunteers treated with endotoxin (up to 1.17% of total protein), as compared to BAL fluids from control patients (<0.005% of total protein). These data suggest that angiostatin may contribute to the endothelial damage observed in ARDS, probably via an increased permeability of the alveolar capillary barrier, allowing for an intra-alveolar processing of its precursor plasminogen.

AB - Acute respiratory distress syndrome (ARDS) is characterized by a disruption of the alveolar-capillary barrier, due to both an epithelial and an endothelial dysfunction. Whereas epithelial apoptosis seems to be mainly mediated by Fas ligand, the mediators of endothelial damage remain to be identified. Angiostatin, a powerful inhibitor of angiogenesis in vivo, also specifically induces apoptosis in endothelial cells. The concentration of various enzymes that cleave angiostatin from plasminogen was reported to be significantly increased in bronchalveolar lavage (BAL) fluids from patients with ARDS. Therefore, in this study, we investigated whether angiostatin was generated during the pulmonary inflammatory response of both healthy subjects challenged with endobronchial endotoxin and in patients with ARDS. We found significantly elevated angiostatin levels in BAL fluids from patients at risk for and with early ARDS (up to 0.022% and 0.018% of total protein, respectively), as well as in BAL fluids from volunteers treated with endotoxin (up to 1.17% of total protein), as compared to BAL fluids from control patients (<0.005% of total protein). These data suggest that angiostatin may contribute to the endothelial damage observed in ARDS, probably via an increased permeability of the alveolar capillary barrier, allowing for an intra-alveolar processing of its precursor plasminogen.

KW - Adult respiratory distress syndrome

KW - Angiostatin

KW - Endothelium

KW - Lipopolysaccharide

UR - http://www.scopus.com/inward/record.url?scp=0036285817&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036285817&partnerID=8YFLogxK

M3 - Article

C2 - 12083503

AN - SCOPUS:0036285817

VL - 87

SP - 966

EP - 971

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 6

ER -