Journal article

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

Shoib S Siddiqui, Chirag Dhar, Venkatasubramaniam Sundaramurthy, Aniruddha Sasmal, Hai Yu, Esther Bandala-Sanchez, Miaomiao Li, Xiaoxiao Zhang, Xi Chen, Leonard C Harrison, Ding Xu, Ajit Varki

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2021

Abstract

Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated..

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