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Tumour Necrosis Factor‐α Induces Neutrophil‐Mediated Injury of Cultured Human Endothelial Cells
Author(s) -
ASMUTH E. J. U.,
LEEUWENBERG J. F. M.,
LINDEN C. J.,
BUURMAN W. A.
Publication year - 1991
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1991.tb01537.x
Subject(s) - umbilical vein , endothelial stem cell , tumor necrosis factor alpha , endothelium , incubation , immunology , human umbilical vein endothelial cell , cytokine , cell , necrosis , neutrophile , inflammation , chemistry , microbiology and biotechnology , biology , medicine , in vitro , pathology , endocrinology , biochemistry
We investigated the ability of TNF‐α to mediate damage of endothelial cells in the presence of neutrophils. by measuring detachment of cultured human umbilical vein endothelial cells (HUVEC). Endothelial cell detachment was increased from 5% to about 75% by the presence of I‐10 ng/ml TNF‐α during incubation with neutrophils, whereas negligible endothelial cell lysis was observed as measured by 51 Cr release. TNF‐α was compared with the cytokines IL‐lα and IFN‐γ and with PMA and LPS. Both TNF‐α and PMA appeared to be strong triggers for neutrophil‐induced endothelial cell detachment, whilst reduced injury was seen after addition of IL‐lα and LPS. IFN‐γ did not induce endothelial cell detachment, but potentiated the effect of both TNF‐α and IL‐lα. TNF‐α‐induced endothelial cell detachment was neutrophil dependent, since pre‐incubation of neutrophils, but not pre‐incubation of endothelial cells with TNF‐α, caused endothelial cell detachment. Thus, TNF‐α‐induced increase in neutrophil‐adhesiveness of HUVEC was found not to be essential for endothelial damage. Pre‐incubation of neutrophils in suspension with TNF‐α induced rapid activation, followed by nearly complete deactivation of neutrophils, as measured by their capacity to induce detachment of endothelial cells after removal of TNF‐α. These results indicate that local presence of TNF‐α might be critical in tissue or organ damage during early, neutrophil‐mediated inflammatory processes, independent of enhanced adhesiveness of endothelium for neutrophils.