The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

Thomsen, Jens Haugbølle; Etzerodt, Anders; Svendsen, Pia; Moestrup, Søren K.

doi:10.1155/2013/523652

Cited by 149 publications

(156 citation statements)

References 120 publications

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“…Lipocalin-2 and haptoglobin are involved in the regulation of iron metabolism, by binding small iron-carrying molecules (siderophores) and hemoglobin (before internalization by CD163 receptor), respectively. Iron capture protects against iron-mediated toxicity (40). This is in agreement with the described iron retention phenotype of M1 macrophages (41), which also has been described in early regenerating muscle (42).…”

Section: Discussionsupporting

confidence: 86%

Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair

Varga

Mounier

Horváth

et al. 2016

The Journal of Immunology

168

212

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Macrophage gene expression determines phagocyte responses and effector functions. Macrophage plasticity has been mainly addressed in in vitro models that do not account for the environmental complexity observed in vivo. In this study, we show that microarray gene expression profiling revealed a highly dynamic landscape of transcriptomic changes of Ly6CposCX3CR1lo and Ly6CnegCX3CR1hi macrophage populations during skeletal muscle regeneration after a sterile damage. Systematic gene expression analysis revealed that the time elapsed, much more than Ly6C status, was correlated with the largest differential gene expression, indicating that the time course of inflammation was the predominant driving force of macrophage gene expression. Moreover, Ly6Cpos/Ly6Cneg subsets could not have been aligned to canonical M1/M2 profiles. Instead, a combination of analyses suggested the existence of four main features of muscle-derived macrophages specifying important steps of regeneration: 1) infiltrating Ly6Cpos macrophages expressed acute-phase proteins and exhibited an inflammatory profile independent of IFN-γ, making them damage-associated macrophages; 2) metabolic changes of macrophages, characterized by a decreased glycolysis and an increased tricarboxylic acid cycle/oxidative pathway, preceded the switch to and sustained their anti-inflammatory profile; 3) Ly6Cneg macrophages, originating from skewed Ly6Cpos cells, actively proliferated; and 4) later on, restorative Ly6Cneg macrophages were characterized by a novel profile, indicative of secretion of molecules involved in intercellular communications, notably matrix-related molecules. These results show the highly dynamic nature of the macrophage response at the molecular level after an acute tissue injury and subsequent repair, and associate a specific signature of macrophages to predictive specialized functions of macrophages at each step of tissue injury/repair.

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Section: Discussionsupporting

confidence: 86%

Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair

Varga

Mounier

Horváth

et al. 2016

The Journal of Immunology

168

212

View full text Add to dashboard Cite

show abstract

“…supported by many studies which demonstrated Hp elevation during bacterial infection, inflammation, tissue destruction, and various malignant diseases [3,32] and also consistent with Sritharanand et al [33] who reported high concentration of Hp in untreated LL patients as compared to healthy controls.…”

Section: Hp Concentrationsupporting

confidence: 82%

Haptoglobin polymorphism, plasma haptoglobin level and ABO blood group in leprosy patients

Seboka¹,

Bekele²,

Nigussie³

et al. 2017

JCLM

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“…CD163 is a scavenger receptor that facilitates binding and endocytosis of hemoglobin‐haptoglobin complexes by monocytic cells, decreasing the cytotoxic load of free hemoglobin that occurs after tissue hemorrhage 10, 11. Recent evidence has shown that CD163 is also upregulated acutely in neurons following ICH both in vivo and in vitro 12.…”

Section: Introductionmentioning

confidence: 99%

Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal edema

Roy-O’Reilly

Zhu

Atadja

et al. 2017

Ann Clin Transl Neurol

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ObjectivePatients with intracerebral hemorrhage (ICH) may elaborate varying degrees of perihematomal edema (PHE), requiring closer monitoring and a higher intensity of treatment. Here, we explore whether the soluble form of CD163, a scavenger receptor responsible for hemoglobin sequestration, can serve as a prognostic biomarker of PHE development and poor outcome after ICH.MethodsOur study cohort was comprised of 51 primary age‐ and sex‐matched ICH patients with moderate‐sized, hypertensive deep hemorrhages. Patients were part of a prospective ICH registry cataloguing admission data along with functional outcomes. We measured sCD163 levels in serial serum and cerebrospinal fluid (CSF) samples obtained at prespecified timepoints. Descriptive statistics, including a generalized estimating equation for longitudinal data, were used to analyze sCD163 in relation to ICH outcomes.ResultsAcute serum sCD163 (<48 h postictus) was significantly elevated in ICH patients compared to both acute neurological event controls (P = <0.001) and healthy controls (P = 0.003). As predicted, acute serum sCD163 levels were significantly associated with both hematoma volume expansion (P = 0.009) and PHE expansion (P = 0.002). Further examination determined that patients with high PHE expansion had poorer modified Rankin Scale scores at discharge (P = 0.024), and circulating sCD163 levels were found to be significantly lower in patients with high‐level PHE expansion.InterpretationAcute sCD163 levels may be a useful biomarker for the acute identification of patients at risk for hematoma expansion, perihematomal edema expansion and poorer short‐term outcomes.

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The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

Cited by 149 publications

References 120 publications

Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair

Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair

Haptoglobin polymorphism, plasma haptoglobin level and ABO blood group in leprosy patients

Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal edema

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