About: Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition

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About: Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition
Creator	Yu, Hai Chen, Xi Varki, Ajit Bandala-Sanchez, Esther Dhar, Chirag »more»
source	BioRxiv
abstract	Blood pH is tightly regulated between 7.35-7.45, with values below 7.3 during sepsis being associated with lactic acidosis, low serum zinc, and release of proinflammatory HMGB1 from activated and/or necrotic cells. Using an ex vivo whole blood system to model lactic acidosis, we show that while HMGB1 does not engage leukocyte receptors at physiological pH, lowering pH with lactic acid facilitates binding. At normal pH, micromolar zinc supports plasma sialoglycoprotein binding by HMGB1, which is markedly reduced when pH is adjusted with lactic acid to sepsis levels. Glycan array studies confirmed zinc and pH-dependent HMGB1 binding to sialoglycans typical of plasma glycoproteins. Thus, proinflammatory effects of HMGB1 are suppressed via plasma sialoglycoproteins until drops in pH and zinc release HMGB1 to trigger downstream immune activation. Significance Statement HMGB1 sequestered by plasma sialoglycoproteins at physiological pH is released when pH and zinc concentrations fall in sepsis.
has issue date	2020-07-15(xsd:dateTime)
bibo:doi	10.1101/2020.07.15.198010
has license	biorxiv
sha1sum (hex)	27adeda086d079045a79724e6268c89c890740d0
schema:url	https://doi.org/10.1101/2020.07.15.198010
resource representing a document's title	Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition
schema:publication	bioRxiv
resource representing a document's body	covid:27adeda086d079045a79724e6268c89c890740d0#body_text
is schema:about of	named entity 'HMGB1' named entity 'Blood pH' named entity 'HMGB1' named entity 'SERUM ZINC' named entity 'DOWNSTREAM' »more»

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