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Pro- and antifibrinolytic properties of human pulmonary microvascular versus artery endothelial cells: impact of endotoxin and tumor necrosis factor-alpha.
Crit Care Med. 2004 Jan; 32(1):217-26.CC

Abstract

OBJECTIVE

Microvascular thrombosis is a common feature of acute inflammatory lung injury, as occurs in sepsis and acute respiratory distress syndrome, but the underlying pathomechanisms are presently not fully understood.

DESIGN

Experimental.

SETTING

University laboratory.

SUBJECTS

Lung endothelial cells.

INTERVENTIONS

We characterized the expression of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) as well as plasminogen activator inhibitor (PAI)-1 and PAI-2 in human endothelial cells (EC) from the microvascular pulmonary circulation (HMVEC-L) and compared it with that of EC from pulmonary artery (HPAEC) and umbilical vein (HUVEC) under baseline conditions and upon stimulation with either tumor necrosis factor-alpha or lipopolysaccharide.

MEASUREMENTS AND MAIN RESULTS

Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were employed for quantification of messenger RNA and protein concentrations. Under baseline conditions, comparable PAI-1 expression was noted in all EC. HPAEC were characterized by significantly higher baseline expression of t-PA and PAI-2 compared with HUVEC and HMVEC-L. In contrast, u-PA messenger RNA concentrations were found to be significantly higher in nonstimulated HMVEC-L compared with HUVEC and HPAEC. In all EC, stimulation with tumor necrosis factor-alpha and lipopolysaccharide increased the expression of PAI-1, PAI-2, and u-PA and decreased t-PA expression. The changes in messenger RNA content were reflected by corresponding changes in the protein concentrations.

CONCLUSIONS

High baseline u-PA expression is a prominent feature of human lung microvascular EC, whereas pulmonary artery EC are characterized by high t-PA concentrations. Microbial and inflammatory challenge provokes up-regulation of PAI-1 and PAI-2 and down-regulation of t-PA in both macro- and microvascular pulmonary EC, which may favor local fibrin deposition.

Authors+Show Affiliations

Department of Internal Medicine, Justus-Liebig-University Giessen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14707582

Citation

Muth, H, et al. "Pro- and Antifibrinolytic Properties of Human Pulmonary Microvascular Versus Artery Endothelial Cells: Impact of Endotoxin and Tumor Necrosis Factor-alpha." Critical Care Medicine, vol. 32, no. 1, 2004, pp. 217-26.
Muth H, Maus U, Wygrecka M, et al. Pro- and antifibrinolytic properties of human pulmonary microvascular versus artery endothelial cells: impact of endotoxin and tumor necrosis factor-alpha. Crit Care Med. 2004;32(1):217-26.
Muth, H., Maus, U., Wygrecka, M., Lohmeyer, J., Grimminger, F., Seeger, W., & Günther, A. (2004). Pro- and antifibrinolytic properties of human pulmonary microvascular versus artery endothelial cells: impact of endotoxin and tumor necrosis factor-alpha. Critical Care Medicine, 32(1), 217-26.
Muth H, et al. Pro- and Antifibrinolytic Properties of Human Pulmonary Microvascular Versus Artery Endothelial Cells: Impact of Endotoxin and Tumor Necrosis Factor-alpha. Crit Care Med. 2004;32(1):217-26. PubMed PMID: 14707582.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pro- and antifibrinolytic properties of human pulmonary microvascular versus artery endothelial cells: impact of endotoxin and tumor necrosis factor-alpha. AU - Muth,H, AU - Maus,U, AU - Wygrecka,M, AU - Lohmeyer,J, AU - Grimminger,F, AU - Seeger,W, AU - Günther,A, PY - 2004/1/7/pubmed PY - 2004/2/13/medline PY - 2004/1/7/entrez SP - 217 EP - 26 JF - Critical care medicine JO - Crit Care Med VL - 32 IS - 1 N2 - OBJECTIVE: Microvascular thrombosis is a common feature of acute inflammatory lung injury, as occurs in sepsis and acute respiratory distress syndrome, but the underlying pathomechanisms are presently not fully understood. DESIGN: Experimental. SETTING: University laboratory. SUBJECTS: Lung endothelial cells. INTERVENTIONS: We characterized the expression of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) as well as plasminogen activator inhibitor (PAI)-1 and PAI-2 in human endothelial cells (EC) from the microvascular pulmonary circulation (HMVEC-L) and compared it with that of EC from pulmonary artery (HPAEC) and umbilical vein (HUVEC) under baseline conditions and upon stimulation with either tumor necrosis factor-alpha or lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were employed for quantification of messenger RNA and protein concentrations. Under baseline conditions, comparable PAI-1 expression was noted in all EC. HPAEC were characterized by significantly higher baseline expression of t-PA and PAI-2 compared with HUVEC and HMVEC-L. In contrast, u-PA messenger RNA concentrations were found to be significantly higher in nonstimulated HMVEC-L compared with HUVEC and HPAEC. In all EC, stimulation with tumor necrosis factor-alpha and lipopolysaccharide increased the expression of PAI-1, PAI-2, and u-PA and decreased t-PA expression. The changes in messenger RNA content were reflected by corresponding changes in the protein concentrations. CONCLUSIONS: High baseline u-PA expression is a prominent feature of human lung microvascular EC, whereas pulmonary artery EC are characterized by high t-PA concentrations. Microbial and inflammatory challenge provokes up-regulation of PAI-1 and PAI-2 and down-regulation of t-PA in both macro- and microvascular pulmonary EC, which may favor local fibrin deposition. SN - 0090-3493 UR - https://www.unboundmedicine.com/medline/citation/14707582/Pro__and_antifibrinolytic_properties_of_human_pulmonary_microvascular_versus_artery_endothelial_cells:_impact_of_endotoxin_and_tumor_necrosis_factor_alpha_ L2 - https://dx.doi.org/10.1097/01.CCM.0000104941.89570.5F DB - PRIME DP - Unbound Medicine ER -