Recombimant TFPI (r-TFPI) reduces the LPS-induced pulmonary vascular injury by inhibiting leukocyte activation

Kazunori Murakami, Kenji Okajima, Perenlei Enkhbaatar, Hirotaka Isobe

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: Tissue factor pathway inhibitor (TFPI) is a physiologic protease inhibitor, which regulates the extrinsic pathway of coagulation by inhibiting F.Xa and F.VIIa. r-TFPI has been shown to inhibit E. coli-induced coagulopathy and the lethal effects. Since activated leukocytes play an important role in such E. coli-induced events, r-TFPI may reduce the lethal effect by inhibiting leukocyte activation. The aim of this study is to examine whether r-TFPI reduces coagulation abnormalities and organ injury by leukocyte activation in rats given LPS. METHODS: LPS (5mg/kg. iv) was injected to induce coagulation abnormalities and acute lung injury. r-TFPI (1mg/kg, iv) was injected 30 minutes prior to the LPS administration. Lung injury was evaluated by measuring lung wet/dry weight ratio 6hrs after LPS injection. Results were compared using Analysis of Variance (ANOVA) and the Scheffe's post hoc test. RESULTS. Leukocytopenia and r-TFPI prevented both LPS-induced pulmonary vascular injury and TNF production, while neither DEGR-VIIa, a competitive inhibitor of F.VIIa, nor DX-9065a, a selective inhibitor of F.Xa did. Pretreatment Safne+LPS r-TFPI+LPS Leutacyts-peala+LPS DEGR-FVIIs+LPS Lung W/D weight ratie 5.11±0.09 5.04±0.06 * 4.98±0.06 * 5.12±0.10 Lung MPO (O/g tissue) 42±6 31±5 * 20±2 * 38±7 Plasma TNF (x101 pg/mLD 7.9±2.3 4.0±1.8 * 2.8±2 * 38±7 FDP[E] [rg/mLI] 95±32 41±8 25±6 * 24±5 * * p<0.05 vs Saline + LPS group. Mean±SD of 6 animal experiments. CONCLUSION: r-TFPI inhibits the LPS-induced coagulation abnormalities and lung injury by inhibiting leukocyte activation.

Original languageEnglish (US)
JournalCritical Care Medicine
Volume27
Issue number1 SUPPL.
StatePublished - 1999
Externally publishedYes

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Vascular System Injuries
Lung Injury
Leukocytes
Escherichia coli
Weights and Measures
Lung
lipoprotein-associated coagulation inhibitor
Acute Lung Injury
Leukopenia
Pulmonary Edema
Protease Inhibitors
Analysis of Variance
Injections
Wounds and Injuries

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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Recombimant TFPI (r-TFPI) reduces the LPS-induced pulmonary vascular injury by inhibiting leukocyte activation. / Murakami, Kazunori; Okajima, Kenji; Enkhbaatar, Perenlei; Isobe, Hirotaka.

In: Critical Care Medicine, Vol. 27, No. 1 SUPPL., 1999.

Research output: Contribution to journalArticle

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abstract = "INTRODUCTION: Tissue factor pathway inhibitor (TFPI) is a physiologic protease inhibitor, which regulates the extrinsic pathway of coagulation by inhibiting F.Xa and F.VIIa. r-TFPI has been shown to inhibit E. coli-induced coagulopathy and the lethal effects. Since activated leukocytes play an important role in such E. coli-induced events, r-TFPI may reduce the lethal effect by inhibiting leukocyte activation. The aim of this study is to examine whether r-TFPI reduces coagulation abnormalities and organ injury by leukocyte activation in rats given LPS. METHODS: LPS (5mg/kg. iv) was injected to induce coagulation abnormalities and acute lung injury. r-TFPI (1mg/kg, iv) was injected 30 minutes prior to the LPS administration. Lung injury was evaluated by measuring lung wet/dry weight ratio 6hrs after LPS injection. Results were compared using Analysis of Variance (ANOVA) and the Scheffe's post hoc test. RESULTS. Leukocytopenia and r-TFPI prevented both LPS-induced pulmonary vascular injury and TNF production, while neither DEGR-VIIa, a competitive inhibitor of F.VIIa, nor DX-9065a, a selective inhibitor of F.Xa did. Pretreatment Safne+LPS r-TFPI+LPS Leutacyts-peala+LPS DEGR-FVIIs+LPS Lung W/D weight ratie 5.11±0.09 5.04±0.06 * 4.98±0.06 * 5.12±0.10 Lung MPO (O/g tissue) 42±6 31±5 * 20±2 * 38±7 Plasma TNF (x101 pg/mLD 7.9±2.3 4.0±1.8 * 2.8±2 * 38±7 FDP[E] [rg/mLI] 95±32 41±8 25±6 * 24±5 * * p<0.05 vs Saline + LPS group. Mean±SD of 6 animal experiments. CONCLUSION: r-TFPI inhibits the LPS-induced coagulation abnormalities and lung injury by inhibiting leukocyte activation.",
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T1 - Recombimant TFPI (r-TFPI) reduces the LPS-induced pulmonary vascular injury by inhibiting leukocyte activation

AU - Murakami, Kazunori

AU - Okajima, Kenji

AU - Enkhbaatar, Perenlei

AU - Isobe, Hirotaka

PY - 1999

Y1 - 1999

N2 - INTRODUCTION: Tissue factor pathway inhibitor (TFPI) is a physiologic protease inhibitor, which regulates the extrinsic pathway of coagulation by inhibiting F.Xa and F.VIIa. r-TFPI has been shown to inhibit E. coli-induced coagulopathy and the lethal effects. Since activated leukocytes play an important role in such E. coli-induced events, r-TFPI may reduce the lethal effect by inhibiting leukocyte activation. The aim of this study is to examine whether r-TFPI reduces coagulation abnormalities and organ injury by leukocyte activation in rats given LPS. METHODS: LPS (5mg/kg. iv) was injected to induce coagulation abnormalities and acute lung injury. r-TFPI (1mg/kg, iv) was injected 30 minutes prior to the LPS administration. Lung injury was evaluated by measuring lung wet/dry weight ratio 6hrs after LPS injection. Results were compared using Analysis of Variance (ANOVA) and the Scheffe's post hoc test. RESULTS. Leukocytopenia and r-TFPI prevented both LPS-induced pulmonary vascular injury and TNF production, while neither DEGR-VIIa, a competitive inhibitor of F.VIIa, nor DX-9065a, a selective inhibitor of F.Xa did. Pretreatment Safne+LPS r-TFPI+LPS Leutacyts-peala+LPS DEGR-FVIIs+LPS Lung W/D weight ratie 5.11±0.09 5.04±0.06 * 4.98±0.06 * 5.12±0.10 Lung MPO (O/g tissue) 42±6 31±5 * 20±2 * 38±7 Plasma TNF (x101 pg/mLD 7.9±2.3 4.0±1.8 * 2.8±2 * 38±7 FDP[E] [rg/mLI] 95±32 41±8 25±6 * 24±5 * * p<0.05 vs Saline + LPS group. Mean±SD of 6 animal experiments. CONCLUSION: r-TFPI inhibits the LPS-induced coagulation abnormalities and lung injury by inhibiting leukocyte activation.

AB - INTRODUCTION: Tissue factor pathway inhibitor (TFPI) is a physiologic protease inhibitor, which regulates the extrinsic pathway of coagulation by inhibiting F.Xa and F.VIIa. r-TFPI has been shown to inhibit E. coli-induced coagulopathy and the lethal effects. Since activated leukocytes play an important role in such E. coli-induced events, r-TFPI may reduce the lethal effect by inhibiting leukocyte activation. The aim of this study is to examine whether r-TFPI reduces coagulation abnormalities and organ injury by leukocyte activation in rats given LPS. METHODS: LPS (5mg/kg. iv) was injected to induce coagulation abnormalities and acute lung injury. r-TFPI (1mg/kg, iv) was injected 30 minutes prior to the LPS administration. Lung injury was evaluated by measuring lung wet/dry weight ratio 6hrs after LPS injection. Results were compared using Analysis of Variance (ANOVA) and the Scheffe's post hoc test. RESULTS. Leukocytopenia and r-TFPI prevented both LPS-induced pulmonary vascular injury and TNF production, while neither DEGR-VIIa, a competitive inhibitor of F.VIIa, nor DX-9065a, a selective inhibitor of F.Xa did. Pretreatment Safne+LPS r-TFPI+LPS Leutacyts-peala+LPS DEGR-FVIIs+LPS Lung W/D weight ratie 5.11±0.09 5.04±0.06 * 4.98±0.06 * 5.12±0.10 Lung MPO (O/g tissue) 42±6 31±5 * 20±2 * 38±7 Plasma TNF (x101 pg/mLD 7.9±2.3 4.0±1.8 * 2.8±2 * 38±7 FDP[E] [rg/mLI] 95±32 41±8 25±6 * 24±5 * * p<0.05 vs Saline + LPS group. Mean±SD of 6 animal experiments. CONCLUSION: r-TFPI inhibits the LPS-induced coagulation abnormalities and lung injury by inhibiting leukocyte activation.

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