Dynamics of a representative DAMP, HMGB1, was examined using vascular endothelial cells (EA.hy926). Histamine concentration-dependently induced the translocation and release of HMGB1 from vascular endothelial cells by the stimulation of H1-receptor subtype, which was mimicked by selective H1- receptor agonist, 2-pyridyl-ethylamine. Mast cell stimulator, compound 48/80, induced an anaphylactic hypotensive shock in rats, associated with the elevation of plasma HMGB1. The treatment with anti-HMGB1 mAb (#10-22) significantly facilitated the recovery from hypotensive shock.
LPS and TNF-α induced a similar HMGB1 release from vascular endothelial cells, associated with the secretion of IL-6 and IL-8. All these responses were inhibited by anti-HMGB1 mAb (#10-22). Taken together, it was concluded that HMGB1 in vascular endothelial cells may respond to many stimulants.
