Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide
OBJECTIVE: Pneumonia is characterized by an acute inflammatory response in the lung, which is frequently associated with changes in coagulation and fibrinolysis in the bronchoalveolar space. Here, we compared the effects of lipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria, and lipopolysaccharide (LPS), in the human bronchoalveolar space.
DESIGN: Controlled in vivo volunteer study.
SETTING: Clinical research unit.
SUBJECTS: Twenty-three healthy nonsmoking male volunteers.
INTERVENTIONS: Sterile saline was instilled into a lung subsegment followed by bronchoscopic instillation of either LTA (Staphylococcus aureus, at a dose of 4, 20, or 100 ng/kg body weight) or LPS (Escherichia coli, 4 ng/kg body weight) into the contralateral lung. Bronchoalveolar lavage fluid was obtained 6 hours thereafter.
MEASUREMENTS AND MAIN RESULTS: Bronchial instillation of LTA- or LPS-activated bronchoalveolar coagulation, as reflected by increases in the levels of thrombin-antithrombin complexes, d-dimer, and soluble tissue factor. Concurrently, LTA and LPS inhibited anticoagulant mechanisms, as indicated by reductions in antithrombin, Protein C, and Activated Protein C concentrations together with elevated levels of soluble thrombomodulin. Both LTA and LPS administration was associated with an inhibition of pulmonary fibrinolysis, as measured by a reduction in plasminogen activator activity and elevated levels of plasminogen activator inhibitor type I.
CONCLUSIONS: This study is the first to describe the effects of LTA on hemostasis in humans, demonstrating that LTA induces similar changes in the human bronchoalveolar space as LPS, characterized by activation of coagulation with concurrent inhibition of anticoagulant and fibrinolytic pathways.
| Errataetall: |
CommentIn: Crit Care Med. 2009 Feb;37(2):774-5. - PMID 19325384 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
Critical care medicine - 37(2009), 2 vom: 28. Feb., Seite 619-25 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hoogerwerf, Jacobien J [VerfasserIn] |
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| Links: |
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| Themen: |
56411-57-5 |
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| Anmerkungen: |
Date Completed 06.05.2009 Date Revised 01.04.2009 published: Print CommentIn: Crit Care Med. 2009 Feb;37(2):774-5. - PMID 19325384 Citation Status MEDLINE |
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| doi: |
10.1097/CCM.0b013e31819584f9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM185477089 |
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| 100 | 1 | |a Hoogerwerf, Jacobien J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide |
| 264 | 1 | |c 2009 | |
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| 500 | |a Date Revised 01.04.2009 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: Crit Care Med. 2009 Feb;37(2):774-5. - PMID 19325384 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: Pneumonia is characterized by an acute inflammatory response in the lung, which is frequently associated with changes in coagulation and fibrinolysis in the bronchoalveolar space. Here, we compared the effects of lipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria, and lipopolysaccharide (LPS), in the human bronchoalveolar space | ||
| 520 | |a DESIGN: Controlled in vivo volunteer study | ||
| 520 | |a SETTING: Clinical research unit | ||
| 520 | |a SUBJECTS: Twenty-three healthy nonsmoking male volunteers | ||
| 520 | |a INTERVENTIONS: Sterile saline was instilled into a lung subsegment followed by bronchoscopic instillation of either LTA (Staphylococcus aureus, at a dose of 4, 20, or 100 ng/kg body weight) or LPS (Escherichia coli, 4 ng/kg body weight) into the contralateral lung. Bronchoalveolar lavage fluid was obtained 6 hours thereafter | ||
| 520 | |a MEASUREMENTS AND MAIN RESULTS: Bronchial instillation of LTA- or LPS-activated bronchoalveolar coagulation, as reflected by increases in the levels of thrombin-antithrombin complexes, d-dimer, and soluble tissue factor. Concurrently, LTA and LPS inhibited anticoagulant mechanisms, as indicated by reductions in antithrombin, Protein C, and Activated Protein C concentrations together with elevated levels of soluble thrombomodulin. Both LTA and LPS administration was associated with an inhibition of pulmonary fibrinolysis, as measured by a reduction in plasminogen activator activity and elevated levels of plasminogen activator inhibitor type I | ||
| 520 | |a CONCLUSIONS: This study is the first to describe the effects of LTA on hemostasis in humans, demonstrating that LTA induces similar changes in the human bronchoalveolar space as LPS, characterized by activation of coagulation with concurrent inhibition of anticoagulant and fibrinolytic pathways | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a de Vos, Alex F |e verfasserin |4 aut | |
| 700 | 1 | |a Levi, Marcel |e verfasserin |4 aut | |
| 700 | 1 | |a Bresser, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a van der Zee, Jaring S |e verfasserin |4 aut | |
| 700 | 1 | |a Draing, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a von Aulock, Sonja |e verfasserin |4 aut | |
| 700 | 1 | |a van der Poll, Tom |e verfasserin |4 aut | |
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