Local activation of the tissue factor-factor VIIa pathway in patients with pneumonia and the effect of inhibition of this pathway in murine pneumococcal pneumonia
OBJECTIVE: The tissue factor (TF)-factor VIIa (FVIIa) complex not only is essential for activation of blood coagulation but also affect the inflammatory response during sepsis. The objective of this study was to determine the role of TF-FVIIa in pneumonia caused by Streptococcus pneumoniae, the most important causative organism in community-acquired pneumonia and a major cause of sepsis.
DESIGN: A controlled, in vivo laboratory study.
SETTING: Research laboratory of a health sciences university.
PATIENTS AND SUBJECTS: Patients with unilateral community-acquired pneumonia and female BALB/c mice.
INTERVENTIONS: Bilateral bronchoalveolar lavage was performed in patients with community-acquired pneumonia. In mice, pneumonia was induced by intranasal inoculation with S. pneumoniae with or without concurrent inhibition of TF-FVIIa by subcutaneous injections of recombinant nematode anticoagulant protein (rNAPc2).
MEASUREMENTS AND MAIN RESULTS: Patients with unilateral community-acquired pneumonia demonstrated elevated concentrations of FVIIa, soluble TF, and thrombin-antithrombin complexes in bronchoalveolar lavage fluid obtained from the infected site compared with the uninfected site. Mice with S. pneumoniae pneumonia displayed increased TF expression and fibrin deposits in lungs together with elevated thrombin-antithrombin complex levels in bronchoalveolar lavage fluid; inhibition of TF-FVIIa by rNAPc2 attenuated the procoagulant response in the lung but did not affect host defense, as reflected by an unaltered outgrowth of pneumococci and an unchanged survival.
CONCLUSIONS: These data suggest that TF-FVIIa activity contributes to activation of coagulation in the lung during pneumococcal pneumonia but does not play an important role in the antibacterial host defense in this murine model.
| Errataetall: |
CommentIn: Crit Care Med. 2006 Jun;34(6):1842-4. - PMID 16714997 |
|---|---|
| Medienart: |
Artikel |
| Erscheinungsjahr: |
2006 |
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| Erschienen: |
2006 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
|---|---|
| Enthalten in: |
Critical care medicine - 34(2006), 6 vom: 07. Juni, Seite 1725-30 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rijneveld, Anita W [VerfasserIn] |
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| Anmerkungen: |
Date Completed 15.06.2006 Date Revised 15.11.2006 published: Print CommentIn: Crit Care Med. 2006 Jun;34(6):1842-4. - PMID 16714997 Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM162109288 |
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| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM162109288 | ||
| 003 | DE-627 | ||
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| 007 | tu | ||
| 008 | 231223s2006 xx ||||| 00| ||eng c | ||
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| 035 | |a (DE-627)NLM162109288 | ||
| 035 | |a (NLM)16625114 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Rijneveld, Anita W |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Local activation of the tissue factor-factor VIIa pathway in patients with pneumonia and the effect of inhibition of this pathway in murine pneumococcal pneumonia |
| 264 | 1 | |c 2006 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 15.06.2006 | ||
| 500 | |a Date Revised 15.11.2006 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: Crit Care Med. 2006 Jun;34(6):1842-4. - PMID 16714997 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: The tissue factor (TF)-factor VIIa (FVIIa) complex not only is essential for activation of blood coagulation but also affect the inflammatory response during sepsis. The objective of this study was to determine the role of TF-FVIIa in pneumonia caused by Streptococcus pneumoniae, the most important causative organism in community-acquired pneumonia and a major cause of sepsis | ||
| 520 | |a DESIGN: A controlled, in vivo laboratory study | ||
| 520 | |a SETTING: Research laboratory of a health sciences university | ||
| 520 | |a PATIENTS AND SUBJECTS: Patients with unilateral community-acquired pneumonia and female BALB/c mice | ||
| 520 | |a INTERVENTIONS: Bilateral bronchoalveolar lavage was performed in patients with community-acquired pneumonia. In mice, pneumonia was induced by intranasal inoculation with S. pneumoniae with or without concurrent inhibition of TF-FVIIa by subcutaneous injections of recombinant nematode anticoagulant protein (rNAPc2) | ||
| 520 | |a MEASUREMENTS AND MAIN RESULTS: Patients with unilateral community-acquired pneumonia demonstrated elevated concentrations of FVIIa, soluble TF, and thrombin-antithrombin complexes in bronchoalveolar lavage fluid obtained from the infected site compared with the uninfected site. Mice with S. pneumoniae pneumonia displayed increased TF expression and fibrin deposits in lungs together with elevated thrombin-antithrombin complex levels in bronchoalveolar lavage fluid; inhibition of TF-FVIIa by rNAPc2 attenuated the procoagulant response in the lung but did not affect host defense, as reflected by an unaltered outgrowth of pneumococci and an unchanged survival | ||
| 520 | |a CONCLUSIONS: These data suggest that TF-FVIIa activity contributes to activation of coagulation in the lung during pneumococcal pneumonia but does not play an important role in the antibacterial host defense in this murine model | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Helminth Proteins |2 NLM | |
| 650 | 7 | |a anti-coagulant protein 5, Ancylostoma caninum |2 NLM | |
| 650 | 7 | |a antithrombin III-protease complex |2 NLM | |
| 650 | 7 | |a Antithrombin III |2 NLM | |
| 650 | 7 | |a 9000-94-6 |2 NLM | |
| 650 | 7 | |a Thromboplastin |2 NLM | |
| 650 | 7 | |a 9035-58-9 |2 NLM | |
| 650 | 7 | |a Peptide Hydrolases |2 NLM | |
| 650 | 7 | |a EC 3.4.- |2 NLM | |
| 650 | 7 | |a Factor VIIa |2 NLM | |
| 650 | 7 | |a EC 3.4.21.21 |2 NLM | |
| 700 | 1 | |a Weijer, Sebastiaan |e verfasserin |4 aut | |
| 700 | 1 | |a Bresser, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Florquin, Sandrine |e verfasserin |4 aut | |
| 700 | 1 | |a Vlasuk, George P |e verfasserin |4 aut | |
| 700 | 1 | |a Rote, William E |e verfasserin |4 aut | |
| 700 | 1 | |a Spek, C Arnold |e verfasserin |4 aut | |
| 700 | 1 | |a Reitsma, Pieter H |e verfasserin |4 aut | |
| 700 | 1 | |a van der Zee, Jaring S |e verfasserin |4 aut | |
| 700 | 1 | |a Levi, Marcel |e verfasserin |4 aut | |
| 700 | 1 | |a van der Poll, Tom |e verfasserin |4 aut | |
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