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Arginase release in hemolytic uremic syndrome affects the vasculature

Friberg Hed, Niklas LU orcid ; Tontanahal, Ashmita LU ; Kristoffersson, Ann-Charlotte LU ; Kaplan, Bernard S. ; Gram, Magnus LU orcid ; Arvidsson, Ida LU and Karpman, Diana LU orcid (2023) 11th VTEC International Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coli Infections
Abstract
Hemolysis is a cardinal feature of hemolytic uremic syndrome (HUS) and during hemolysis excess arginase 1 is released from erythrocytes. Increased arginase activity leads to reduced arginine, as it is converted to urea and ornithine, and thereby reduced nitric oxide bioavailability, with secondary vascular injury. In this study we investigated arginase release in HUS patients and laboratory models. Two separate cohorts of patients (n=47 in total) with HUS associated with Shiga toxin-producing enterohemorrhagic E. coli (EHEC) and pediatric controls (n=35) were investigated. HUS patients had excessively high arginase 1 levels and activity (conversion to urea and ornithine) in plasma/serum during the acute phase, compared to remission and... (More)
Hemolysis is a cardinal feature of hemolytic uremic syndrome (HUS) and during hemolysis excess arginase 1 is released from erythrocytes. Increased arginase activity leads to reduced arginine, as it is converted to urea and ornithine, and thereby reduced nitric oxide bioavailability, with secondary vascular injury. In this study we investigated arginase release in HUS patients and laboratory models. Two separate cohorts of patients (n=47 in total) with HUS associated with Shiga toxin-producing enterohemorrhagic E. coli (EHEC) and pediatric controls (n=35) were investigated. HUS patients had excessively high arginase 1 levels and activity (conversion to urea and ornithine) in plasma/serum during the acute phase, compared to remission and controls. Arginase 1 levels correlated with lactate dehydrogenase activity, indicating hemolysis, as well as the need for dialysis treatment. Patients also exhibited high levels of plasma alpha-1-microglobulin, a heme scavenger. Two mouse models were used, mice were challenged intragastrically with E. coli O157:H7 or injected intraperitoneally with Shiga toxin 2. Both models exhibited significantly elevated plasma arginase 1 levels and activity. Arginase 1 levels correlated with lactate dehydrogenase activity and alpha-1-microglobulin in the plasma of EHEC-infected mice. In vitro perfusion of Shiga toxin 2- and E. coli O157-lipopolysaccharide-stimulated human blood cells combined with ADAMTS13-deficient plasma over glomerular endothelial cells induced hemolysis and the release of bioactive arginase 1. The high levels of arginase released during HUS could thereby contribute to microvascular injury during HUS. (Less)
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Contribution to conference
publication status
published
subject
conference name
11th VTEC International Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coli Infections
conference location
Banff, Canada
conference dates
2023-05-07 - 2023-05-10
language
English
LU publication?
yes
id
537359cf-5212-4654-9290-c5b9dbf016d0
date added to LUP
2024-04-22 15:44:34
date last changed
2024-04-24 02:58:58
@misc{537359cf-5212-4654-9290-c5b9dbf016d0,
  abstract     = {{Hemolysis is a cardinal feature of hemolytic uremic syndrome (HUS) and during hemolysis excess arginase 1 is released from erythrocytes. Increased arginase activity leads to reduced arginine, as it is converted to urea and ornithine, and thereby reduced nitric oxide bioavailability, with secondary vascular injury. In this study we investigated arginase release in HUS patients and laboratory models. Two separate cohorts of patients (n=47 in total) with HUS associated with Shiga toxin-producing enterohemorrhagic E. coli (EHEC) and pediatric controls (n=35) were investigated. HUS patients had excessively high arginase 1 levels and activity (conversion to urea and ornithine) in plasma/serum during the acute phase, compared to remission and controls. Arginase 1 levels correlated with lactate dehydrogenase activity, indicating hemolysis, as well as the need for dialysis treatment. Patients also exhibited high levels of plasma alpha-1-microglobulin, a heme scavenger. Two mouse models were used, mice were challenged intragastrically with E. coli O157:H7 or injected intraperitoneally with Shiga toxin 2. Both models exhibited significantly elevated plasma arginase 1 levels and activity. Arginase 1 levels correlated with lactate dehydrogenase activity and alpha-1-microglobulin in the plasma of EHEC-infected mice. In vitro perfusion of Shiga toxin 2- and E. coli O157-lipopolysaccharide-stimulated human blood cells combined with ADAMTS13-deficient plasma over glomerular endothelial cells induced hemolysis and the release of bioactive arginase 1. The high levels of arginase released during HUS could thereby contribute to microvascular injury during HUS.}},
  author       = {{Friberg Hed, Niklas and Tontanahal, Ashmita and Kristoffersson, Ann-Charlotte and Kaplan, Bernard S. and Gram, Magnus and Arvidsson, Ida and Karpman, Diana}},
  language     = {{eng}},
  month        = {{05}},
  title        = {{Arginase release in hemolytic uremic syndrome affects the vasculature}},
  year         = {{2023}},
}