HMGB1 release in co-cultures of porcine endothelial and human T cells.
Xenotransplantation
; 14(6): 636-41, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-17991152
ABSTRACT
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-alpha) 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Linfócitos T
/
Proteína HMGB1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Xenotransplantation
Ano de publicação:
2007
Tipo de documento:
Article