id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-102668-1yc38ok1	Siddiqui, Shoib S.	Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition	2020-07-15		.txt	text/plain	5387	292	50	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. The mechanisms underlying lethality associated with low blood pH are not clear, but include low zinc levels and release from apoptotic or necrotic cells of HMGB1, a damageassociated molecular pattern (DAMP) defined as one of the late mediators of sepsis, further upregulating many other proinflammatory cytokines (10) (11) (12) . Here we report one plausible explanation for the tight regulation of blood pH between 7.35-7.45, showing that even a slight reduction to pH 7.2 abolishes the zinc-dependent sequestration of HMGB1 by plasma sialoglycoproteins, releasing it to bind to activating receptors on neutrophils. During sepsis, the drop in pH and zinc concentration of the blood leads to disruption of HMGB1's binding with sialic acid, enabling the free HMGB1 to bind with TLRs and RAGE present on immune cells and the endothelium.	./cache/cord-102668-1yc38ok1.txt	./txt/cord-102668-1yc38ok1.txt