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Tumor necrosis factor α and interleukin 1 α enhance lipopolysaccharide‐mediated bovine endothelial cell injury
Author(s) -
Sharma Smita A.,
Olchowy Timothy W.J.,
Yang Zhengang,
Breider Mike A.
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.51.6.579
Subject(s) - lipopolysaccharide , tumor necrosis factor alpha , biology , interleukin , in vitro , macrophage , cytokine , immunology , endothelial stem cell , receptor antagonist , cytotoxic t cell , alveolar macrophage , microbiology and biotechnology , receptor , pharmacology , antagonist , biochemistry
Alveolar macrophages (AMs) are important in the host response to aerogenous pulmonary bacterial infections, such as Pasteurella haemolytica–induced pneumonia in cattle. Previous work has shown that AMs enhance P. haemolytica –mediated pulmonary endothelial cell (EC) damage in vitro. The purpose of this study was to determine the mechanism of AM‐enhanced EC damage using an in vitro AM‐EC coculture system consisting of AMs cultured on culture plate insert membranes and ECs in the underlying chamber. The addition of lipopolysaccharide (LPS) to the culture plate insert chamber resulted in EC damage indicated by 51 Cr release, which was enhanced in the presence of AMs. To determine the role of AM‐secreted cytokines, recombinant human interleukin 1 α (IL‐1) or tumor necrosis factor α (TNF) was added to ECs simultaneously with varying concentrations of LPS. Although TNF and IL‐1 alone had only marginal toxic effects on ECs, the simultaneous treatment of TNF or IL‐1 with LPS greatly increased the LPS cytotoxic effect on ECs. In addition, IL‐1 receptor antagonist eliminated the IL‐1 enhancement of LPS‐mediated EC toxicity. These results suggest that macrophage‐secreted cytokines synergistically enhance LPS‐mediated pulmonary EC damage.