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HMGB1 release in co‐cultures of porcine endothelial and human T cells
Author(s) -
Kawahara Koichi,
Setoyama Kentaro,
Kikuchi Kiyoshi,
Biswas Kamal Krishna,
Kamimura Ryozo,
Iwata Masahiro,
Ito Takashi,
Morimoto Yoko,
Hashiguchi Teruto,
Takao Sonshin,
Maruyama Ikuro
Publication year - 2007
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2007.00434.x
Subject(s) - hmgb1 , rage (emotion) , extracellular , microbiology and biotechnology , cytokine , tumor necrosis factor alpha , receptor , chemistry , biology , inflammation , immunology , biochemistry , neuroscience
High mobility group box‐1 (HMGB1) protein, primarily from the nucleus, is released into the extracellular milieu either passively by necrotic or damaged cells, or actively by secretion from monocytes/macrophages. Extracellular HMGB1 acts as a potent inflammatory stimulator by promoting cytokine (for example, tumor necrosis factor‐α) production, and also has pro‐coagulant activity. The signaling pathway initiated by receptor for advanced glycation end‐product (RAGE), which is the HMGB1 receptor, also induces complement activation. Recent studies have implicated HMGB1 in acute cardiac allograft rejection, and have identified infiltrating T cells and other damaged cells as its main sources. HMGB1 blockade using the anti‐HMGB1 antibody HMGB1 box‐A (amino‐terminal region) and soluble RAGE rescues mice from acute rejection. We therefore studied the release of HMGB1 in co‐cultures of porcine aortic endothelial cells (PAEC) and human leukocytes. Human T cells, but not B cells, monocytes or neutrophils, stimulated significant HMGB1 release in culture with PAEC; this activity required cell–cell contact and was dose‐dependent, as determined by Western blotting. The released HMGB1 originated from both cell types, as immunofluorescent microscopy showed that it was present in the cytosol of PAEC in contact with T cells, and had disappeared from the T‐cell nuclei. These results demonstrate that direct interactions between PAEC and T cells might be a key factor in triggering HMGB1 release, which suggests that HMGB1 is associated with graft rejection in the early phase.