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

Shoib Sarwar Siddiqui | Zendy; Chirag Dhar | Zendy; Venkatasubramaniam Sundaramurthy | Zendy; Aniruddha Sasmal | Zendy; Hai Yu | Zendy; Esther BandalaSanchez | Zendy; Miaomiao Li | Zendy; Xiaoxiao Zhang | Zendy; Xi Chen | Zendy; Leonard C. Harrison | Zendy; Ding Xu | Zendy; Ajit Varki | Zendy

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

Author(s) -

Shoib Sarwar Siddiqui,

Chirag Dhar,

Venkatasubramaniam Sundaramurthy,

Aniruddha Sasmal,

Hai Yu,

Esther BandalaSanchez,

Miaomiao Li,

Xiaoxiao Zhang,

Xi Chen,

Leonard C. Harrison,

Ding Xu,

Ajit Varki

Publication year - 2021

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.2018090118

Subject(s) - proinflammatory cytokine , sepsis , hmgb1 , zinc , acidosis , immunology , inflammation , chemistry , medicine , biology , organic chemistry

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

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