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Perioperative elastase activity in cardiac surgery and its role in endothelial leakage
M Scholz1, G Wimmer-Greinecker, A Simon
1Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe-University, 60590 Frankfurt am Main, Germany. mscholz@em.uni-frankfurt.de
Objective And Design:
The functional activity and pathophysiological effects of polymorphonuclear elastase (PMNE) in cardiac surgery patients are unknown. This in vitro study was done to evaluate whether PMNE activity in patient blood samples may be correlated with decreased endothelial wall integrity.
Methods And Subjects:
PMNE was serially analyzed by PMNE activity in plasma samples from 40 high risk cardiac surgery patients. Endothelial cell cultures were used to study the influence of patient serum on the intercellular integrity.
Results:
Ex vivo, samples with high PMNE activity (>1.0 mg/ ml), found in 14 patients (35%), neither induced hyperpermeability in cultured endothelial cells nor resulted in intracellular redistribution of the junction molecules cadherin-5 or beta-catenin. However, pretreatment of endothelial cells with these samples but not with low activity (<0.5 mg/ml) samples augmented neutrophil transendothelial migration (>20-fold) in conjunction with formation of intercellular gaps and irregular membrane-associated beta-catenin staining. Neutrophil transmigration was inhibited by blocking neutrophil beta1 integrin but not by the proteinase inhibitor methoxysuccinyl-Ala-Ala-Pro-Ala.
Conclusions:
Augmented PMNE activity in cardiac surgery patients does not directly induce endothelial leakage but may indirectly promote neutrophil extravasation and thus perioperative endothelial hyperpermeability.
Insights
High polymorphonuclear elastase (PMNE) activity in cardiac surgery patients doesn't directly damage endothelial cells. However, it indirectly increases neutrophil migration, potentially causing perioperative endothelial hyperpermeability.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Cell Biology
Background:
- The role of polymorphonuclear elastase (PMNE) in cardiac surgery patients remains unclear.
- Investigating PMNE's impact on endothelial integrity is crucial for understanding perioperative complications.
Purpose of the Study:
- To determine the functional activity and pathophysiological effects of PMNE in cardiac surgery patients.
- To evaluate the correlation between PMNE activity and endothelial wall integrity in vitro.
Main Methods:
- Serial analysis of PMNE activity in plasma samples from 40 high-risk cardiac surgery patients.
- Utilized endothelial cell cultures to assess the influence of patient serum on intercellular integrity.
Main Results:
- High PMNE activity (>1.0 mg/ml) in 35% of patients did not directly cause endothelial hyperpermeability or junction molecule redistribution.
- Pretreatment with high PMNE activity serum augmented neutrophil transendothelial migration (>20-fold), leading to intercellular gaps and altered beta-catenin staining.
- Neutrophil transmigration was inhibited by blocking neutrophil beta1 integrin.
Conclusions:
- Elevated PMNE activity in cardiac surgery patients does not directly induce endothelial leakage.
- PMNE may indirectly promote neutrophil extravasation, contributing to perioperative endothelial hyperpermeability.
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