Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis

Significance Sepsis is a condition wherein microbial infection leads to life-threatening systemic hyperactivation of innate immunity. Blood pH normally maintained tightly between 7.35 and 7.45, lactic acidosis with <7.3 indicates poor prognosis in sepsis, also associated low zinc levels. Release HMGB1 from activated and/or necrotic tissues plays pivotal role triggering the proinflammatory cascade late sepsis. Using an vitro whole-blood assay, we observed that cannot mediate activity at physiological concentrations. This due zinc-dependent association sialoglycoproteins, thereby preventing its binding receptors. Thus, drop concentration sepsis can release sequestered trigger inflammatory cascade.