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Hyperglycemia induces inflammatory response of human macrophages to CD163-mediated scavenging of hemoglobin-haptoglobin complexes

Hyperglycemia, a hallmark of diabetes, can induce inflammatory programming of macrophages. The macrophage scavenger receptor CD163 internalizes and degrades hemoglobin-haptoglobin (Hb-Hp) complexes built due to intravascular hemolysis. Clinical studies have demonstrated a correlation between impaire...

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Main Authors: Matuschik, Laura (Author) , Riabov, Vladimir (Author) , Schmuttermaier, Christina (Author) , Sevastyanova, Tatyana (Author) , Weiß, Christel (Author) , Klüter, Harald (Author) , Kzhyshkowska, Julia (Author)
Format: Article (Journal)
Language:English
Published: 26 January 2022
In: International journal of molecular sciences
Year: 2022, Volume: 23, Issue: 3, Pages: 1-19
ISSN:1422-0067
DOI:10.3390/ijms23031385
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms23031385
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/23/3/1385
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Author Notes:Laura Matuschik, Vladimir Riabov, Christina Schmuttermaier, Tatyana Sevastyanova, Christel Weiss, Harald Klüter and Julia Kzhyshkowska
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Summary:Hyperglycemia, a hallmark of diabetes, can induce inflammatory programming of macrophages. The macrophage scavenger receptor CD163 internalizes and degrades hemoglobin-haptoglobin (Hb-Hp) complexes built due to intravascular hemolysis. Clinical studies have demonstrated a correlation between impaired scavenging of Hb-Hp complexes via CD163 and diabetic vascular complications. Our aim was to identify whether hyperglycemia is able to amplify inflammation via Hb-Hp complex interactions with the immune system. M(IFNγ), M(IL-4), and control M0 macrophages were differentiated out of primary human monocytes in normo- (5 mM) and hyperglycemic (25 mM) conditions. CD163 gene expression was decreased 5.53 times in M(IFNγ) with a further decrease of 1.99 times in hyperglycemia. Hyperglycemia suppressed CD163 surface expression in M(IFNγ) (1.43 times). Flow cytometry demonstrated no impairment of Hb-Hp uptake in hyperglycemia. However, hyperglycemia induced an inflammatory response of M(IFNγ) to Hb-Hp1-1 and Hb-Hp2-2 uptake with different dynamics. Hb-Hp1-1 uptake stimulated IL-6 release (3.03 times) after 6 h but suppressed secretion (5.78 times) after 24 h. Contrarily, Hb-Hp2-2 uptake did not affect IL-6 release after 6h but increased secretion after 24 h (3.06 times). Our data show that hyperglycemia induces an inflammatory response of innate immune cells to Hb-Hp1-1 and Hb-Hp2-2 uptake, converting the silent Hb-Hp complex clearance that prevents vascular damage into an inflammatory process, hereby increasing the susceptibility of diabetic patients to vascular complications.
Item Description:Gesehen am 14.05.2024
Physical Description:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms23031385

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