Cardiac surgery with extracorporeal circulation: neutrophil transendothelial migration is mediated by beta1 integrin (CD29) in the presence of TNF-alpha.
Cardiac surgery with extracorporeal circulation is associated with neutrophil activation, inflammation, and edema. Endothelial hyperpermeability elicited by the interaction of activated neutrophils and/or cytokines with endothelial cells may be critical in this regard. However, the immune and cellular mechanisms involved are not fully understood. Cocultures with human endothelial cells and neutrophils from cardiac surgery patients were used to evaluate the role of beta1 integrin activity and the proinflammatory cytokine tumor necrosis factor (TNF)-alpha in neutrophil transendothelial migration and in impairment of the integrity of endothelial cell-to-cell contacts. Blocking of CD29 (heavy chain of beta1 integrins) totally prevented neutrophil adhesion and transendothelial migration. Pretreatment of neutrophils with either a CD29-stimulating monoclonal antibody or the addition of TNF-alpha (0.1-10 U/ml) to the coculture failed to induce transendothelial migration. However, coculture of endothelial cells with CD29-stimulated neutrophils in the presence of 0.1-10 U/ml TNF-alpha strongly induced neutrophil transmigration. CD29/TNF-alpha-mediated transmigration was associated with intracellular redistribution of endothelial beta-catenin. We further showed that CD29/TNF-alpha-mediated effects involved PI3K and tyrosine kinase-dependent signaling via MAPK but were independent of nuclear transcription factor (NF)-kappaB activity. Inhibition of CD29/TNF-alpha might be a therapeutic option to limit endothelial dysfunction following cardiac surgery with extracorporeal circulation.
Scholz
Martin
M
Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany. m.scholz@em.uni-frankfurt.de
Nowak
Peter
P
Schuller
Alina
A
Margraf
Stefan
S
Blaheta
Roman
R
Cinatl
Jindrich
J
Windolf
Joachim
J
Moritz
Anton
A
D002465:Cell Movement; D002478:Cells, Cultured; D001026:Coronary Artery Bypass; D004730:Endothelium, Vascular; D005112:Extracorporeal Circulation; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology
D019012:Integrin beta1; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases