CD163, a Hemoglobin/Haptoglobin Scavenger Receptor, After Intracerebral Hemorrhage: Functions in Microglia/Macrophages Versus Neurons

Garton, Thomas; Keep, Richard F.; Hua, Ya; Xi, Guohua

doi:10.1007/s12975-017-0535-5

Cited by 47 publications

(43 citation statements)

References 38 publications

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“…Due to its role in the endocytosis of hemoglobin into cells like neurons that lack the appropriate iron sequestration systems, CD163 has been suggested to be a target for reducing neuronal injury after IVH 82 . However, microglial and macrophage CD163 has been shown to be beneficial for clearing hemoglobin from the extracellular space and thereby decreasing injury after cerebral hemorrhage 83 .…”

Section: Ivh-induced Brain Injurymentioning

confidence: 99%

Challenges for intraventricular hemorrhage research and emerging therapeutic targets

Garton

Hua

Xiang

et al. 2017

Expert Opinion on Therapeutic Targets

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Introduction – Intraventricular hemorrhage (IVH) affects both premature infants and adults. In both demographics, it has high mortality and morbidity. There is no FDA approved therapy that improves neurological outcome in either population highlighting the need for additional focus on therapeutic targets and treatments emerging from preclinical studies. Areas Covered – IVH induces both initial injury linked to the physical effects of the blood (mass effect) and secondary injury linked to the brain response to the hemorrhage. Preclinical studies have identified multiple secondary injury mechanisms following IVH, and particularly the role of blood components (e.g. hemoglobin, iron, thrombin). This review, with an emphasis on pre-clinical IVH research, highlights therapeutic targets and treatments that may be of use in prevention, acute care, or repair of damage. Expert Opinion – An IVH is a potentially devastating event. Progress has been made in elucidating injury mechanisms, but this has still to translate to the clinic. Some pathways involved in injury also have beneficial effects (coagulation cascade/inflammation). A greater understanding of the downstream pathways involved in those pathways may allow therapeutic development. Iron chelation (deferoxamine) is in clinical trial for intracerebral hemorrhage and preclinical data suggest it may be a potential treatment for IVH.

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Section: Ivh-induced Brain Injurymentioning

confidence: 99%

Challenges for intraventricular hemorrhage research and emerging therapeutic targets

Garton

Hua

Xiang

et al. 2017

Expert Opinion on Therapeutic Targets

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“…However, emerging findings suggest equally important protective features. Several studies have defined that hemoglobin‐derived heme could reshape the phenotype of macrophages, which is implicated in reduction of atherosclerosis and tissue injury in the brain 10,11,13‐15 . Certain amounts of heme are often exposed to the intestinal microenvironment in IBD.…”

Section: Discussionmentioning

confidence: 99%

“…Tissue micro‐environment is crucial for shaping the identities of macrophages 8,9 . Heme, a metabolite of erythrocyte degradation, was reported to play protective roles in hemorrhagic diseases like stroke and atherosclerosis by providing anti‐inflammatory features and restorative functions for macrophages 10‐15 . Bleeding within the mucosa is commonly seen in both patients and mice with UC, resulting in heme accumulating in intestine mucosal 16 .…”

Section: Introductionmentioning

confidence: 99%

Heme protects intestinal mucosal barrier in DSS‐induced colitis through regulating macrophage polarization in both HO‐1‐dependent and HO‐1‐independent way

Zhang

et al. 2020

FASEB j.

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Hemoglobin‐derived heme was reported to play protective roles in hemorrhagic diseases by modulating the macrophages toward recovery. Mucosal bleeding is one of the pathological features of inflammatory bowel diseases (IBD). However, whether heme provides anti‐inflammatory profiles in macrophages, thus contributing to the intestinal mucosal barrier protection, is unclear. In the current study, we investigated the beneficial effects of heme on DSS‐induced colitis mice and explored the underlying mechanisms. In vivo, systemic heme supplementation by hemin injection relieved intestinal inflammation and remedied intestinal mucosal barrier damage by correcting abnormal intestinal macrophage polarization. In vitro, we confirmed the reciprocally regulating effects of hemin on M1/M2 macrophage polarization in BMDM. Intriguingly, with knockdown of HO‐1, the inhibiting effects of hemin on M1 polarization were maintained, while the promoting effects on M2 polarization were reversed. Further research proved that hemin repressed the inflammatory profiles in macrophages through inhibiting the translocation of NF‐κB p65 by disrupting IRF5‐NF‐κB p65 complex formation in Spi‐C‐dependent way. In conclusion, these results showed that the modification of colon tissue microenvironment with heme supplementation plays a protective role in DSS‐induced colitis mice through regulating the macrophage polarization in both HO‐1‐dependent and HO‐1‐independent way, indicating a new choice to therapeutically modulate the macrophage function and prevent IBD.

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“…80 Garton et al reported that the IL-10 mRNA expression levels associate with an increase in either the diastolic blood pressure or the glycated hemoglobin (HbA1c) values. Also, mRNA expression of CD163, which contributes to anti-inflammatory signals via IL-10 mediated-protein kinase B pathway, 90 has decreased in patients with obesity and diabetes, which is associated with fasting insulin, HbA1c, and endothelial function index (pales wave velocity (PWV)). 89 Increasing TNF-α production following LPS stimulation has also associated with TG and insulin concentrations in OB individuals without obesity-induced comorbidities.…”

Section: Vessel Patrollingmentioning

confidence: 99%

<p>The Exercise Training Modulatory Effects on the Obesity-Induced Immunometabolic Dysfunctions</p>

Soltani¹,

Marandi²,

Kazemi³

et al. 2020

DMSO

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Reduced physical activity rate in people's lifestyle is a global concern associated with the prevalence of health disorders such as obesity and metabolic disturbance. Ample evidence has indicated a critical role of the immune system in the aggravation of obesity. The type, duration, and production of adipose tissue-released mediators may change subsequent inactive lifestyle-induced obesity, leading to the chronic systematic inflammation and monocyte/macrophage (MON/MФ) phenotype polarization. Preliminary adipose tissue expansion can be inhibited by changing the lifestyle. In this context, exercise training is widely recommended due to a definite improvement of energy balance and the potential impacts on the inflammatory signaling cascades. How exercise training affects the immune system has not yet been fully elucidated, because its anti-inflammatory, pro-inflammatory, or even immunosuppressive impacts have been indicated in the literature. A thorough understanding of the mechanisms triggered by exercise can suggest a new approach to combat metainflammation-induced metabolic diseases. In this review, we summarized the obesityinduced inflammatory pathways, the roles of MON/MФ polarization in adipose tissue and systemic inflammation, and the underlying inflammatory mechanisms triggered by exercise during obesity.

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CD163, a Hemoglobin/Haptoglobin Scavenger Receptor, After Intracerebral Hemorrhage: Functions in Microglia/Macrophages Versus Neurons

Cited by 47 publications

References 38 publications

Challenges for intraventricular hemorrhage research and emerging therapeutic targets

Challenges for intraventricular hemorrhage research and emerging therapeutic targets

Heme protects intestinal mucosal barrier in DSS‐induced colitis through regulating macrophage polarization in both HO‐1‐dependent and HO‐1‐independent way

<p>The Exercise Training Modulatory Effects on the Obesity-Induced Immunometabolic Dysfunctions</p>

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