Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli

Buechler, Christa; Ritter, Mirko; Orsó, Evelyn; Langmann, Thomas; Klucken, Jochen; Schmitz, Gerd

doi:10.1002/jlb.67.1.97

Cited by 626 publications

(565 citation statements)

References 45 publications

(75 reference statements)

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“…16 Here we confirm these findings and show that HLA-DR/DP/DQ loss in Dex-treated patients is independent of disease grade (Figure 6A). Consistent with the fact that the gene for CD163 is glucocorticoid-regulated, 18,22,29 we found that CD163 was expressed on a higher percentage of circulating CD14+ monocytes in Dex-treated low and high-grade glioma patients (Figure 6B). In contrast, we see no change in the frequency of the commonly used MDSC marker CD33 (Figure 6C) or the T cell suppressive marker PD-L1 (Figure 6D), indicating that Dex doesn’t universally suppress surface protein expression, but may have specific targets.…”

Section: Resultssupporting

confidence: 84%

“…CD163, a common maker of tumor associated myeloid cells (TAMs), 17 functions as a hemoglobin-haptoglobin scavenger receptor, and is up-regulated on the surface of macrophages, monocytes, and microglia in response to anti-inflammatory cytokines such as IL-10, 18,19 and glucocorticoids such as Dex. 20-22 A recent study evaluating grades II-IV astrocytomas demonstrates that CD163 mRNA expression increases with increasing grade of astrocytoma, and that CD163+ cells produce IL-10 in the GBM tumor microenvironment.…”

Section: Resultsmentioning

confidence: 99%

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Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma

et al. 2018

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Efforts to reduce immunosuppression in the solid tumor microenvironment by blocking the recruitment or polarization of tumor associated macrophages (TAM), or myeloid derived suppressor cells (MDSCs), have gained momentum in recent years. Expanding our knowledge of the immune cell types, cytokines, or recruitment factors that are associated with high-grade disease, both within the tumor and in circulation, is critical to identifying novel targets for immunotherapy. Furthermore, a better understanding of how therapeutic regimens, such as Dexamethasone (Dex), chemotherapy, and radiation, impact these factors will facilitate the design of therapies that can be targeted to the appropriate populations and retain efficacy when administered in combination with standard of care regimens. Here we perform quantitative analysis of tissue microarrays made of samples taken from grades I-III astrocytoma and glioblastoma (GBM, grade IV astrocytoma) to evaluate infiltration of myeloid markers CD163, CD68, CD33, and S100A9. Serum, flow cytometric, and Nanostring analysis allowed us to further elucidate the impact of Dex treatment on systemic biomarkers, circulating cells, and functional markers within tumor tissue. We found that common myeloid markers were elevated in Dex-treated grade I astrocytoma and GBM compared to non-neoplastic brain tissue and grade II-III astrocytomas. Cell frequencies in these samples differed significantly from those in Dex-naïve patients in a pattern that depended on tumor grade. In contrast, observed changes in serum chemokines or circulating monocytes were independent of disease state and were due to Dex treatment alone. Furthermore, these changes seen in blood were often not reflected within the tumor tissue.Conclusions: Our findings highlight the importance of considering perioperative treatment as well as disease grade when assessing novel therapeutic targets or biomarkers of disease.

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma

et al. 2018

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“…Macrophage CD163 expression that is known to be regulated by anti-as well as pro-inflammatory stimuli 42 was not apparently altered by obesity (Figure 1c). This finding is somewhat surprising, as factors inducing CD163 such as interleukin-6 and tumor necrosis factor-a are elevated in the obese adipose tissue, but are in accordance with previous data on CD163 surface expression, which did not correlate with BMI in a small cross-sectional study.…”

Section: Discussionmentioning

confidence: 93%

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

et al. 2009

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Objective: Insulin resistance in visceral obesity is substantially driven by adipose tissue inflammation, particularly by macrophages accumulating in obese adipose tissue. In contrast, adipose tissue macrophages express the hemoglobin scavenger receptor (CD163) and heme oxygenase-1 (gene: HMOX1) that together protect from oxidative stress. Our aim was to evaluate the expression of CD163 and HMOX1 in intra-abdominal visceral (omental) and subcutaneous adipose tissue as well as circulating soluble CD163 concentrations in human obesity and its association with adipose tissue inflammation, body fat distribution and insulin resistance. Methods: CD163, HMOX1 and CD68 mRNA expression in visceral and subcutaneous adipose tissue, serum concentration of soluble CD163 in morbidly obese patients (body mass index (BMI) 440 kg m À2 ), who underwent laparoscopic surgery for gastric banding (n ¼ 20), matched for age and sex to controls (BMIo30 kg m À2 ; n ¼ 20) was analyzed. Results: CD163 expression was highly upregulated in human adipose tissue and soluble CD163 serum concentration was elevated in obese vs lean subjects. HMOX1 was upregulated in adipose tissue by obesity as well and expressed predominantly in macrophages. Although CD163 expression strictly correlated with macrophage abundance, HMOX1 was additionally upregulated within macrophages. This upregulation was significantly lower in visceral compared with subcutaneous adipose tissue. Strikingly, relative visceral adipose tissue expression of HMOX1 negatively correlated with waist-to-hip ratio and the homeostasis model assessment of insulin resistance (both P ¼ 0.024). Conclusions: Visceral obesity is associated with defective upregulation of heme oxygenase-1 in visceral adipose tissue. A lack of this antioxidative and anti-inflammatory enzyme in visceral adipose tissue could contribute to the development of insulin resistance.

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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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Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli

Cited by 626 publications

References 45 publications

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal edema

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