CCR8 Signaling Influences Toll-Like Receptor 4 Responses in Human Macrophages in Inflammatory Diseases

Reimer, Martina Kvist; Brange, Charlotte; Rosendahl, Alexander

doi:10.1128/cvi.05275-11

Cited by 20 publications

(15 citation statements)

References 36 publications

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“…For example, the high-affinity CCL1 receptor, CCR8, has previously been shown to be highly expressed on AMs and its expression has been associated with phagocytic macrophages [21]. Furthermore, CCR8 is upregulated on AMs from COPD patients and is reported to impact macrophage adhesion, chemotaxis, ROS generation and cytokine production [22]. In this study we report that although CCR8 is highly expressed on primary AMs, it is essentially absent on all evaluated macrophage surrogates.…”

Section: Discussionmentioning

confidence: 54%

Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

et al. 2012

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BackgroundAlveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansion in-vitro and therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60) are frequently used to model macrophage function.MethodsThe availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR) and ion channel expression in alveolar macrophages and their widely used surrogates.ResultsThe complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates.ConclusionsThe data described in this report provides insight into the appropriate choice of cell models for investigating macrophage biology and highlights the importance of confirming experimental data in primary alveolar macrophages.

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Section: Discussionmentioning

confidence: 54%

Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

et al. 2012

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“…Another observation was made in detecting the cellular cluster area, which was reduced via PMA or plasma. Peritoneal macrophages are able to adhere and cluster via the chemokine-receptor system CCL1/CCR8 [79], and this system is mainly utilized by cells of the M2 phenotype [80], pointing to a rather pro-inflammatory ROS-induced phenotype.…”

Section: Discussionmentioning

confidence: 99%

Plasma-Derived Reactive Species Shape a Differentiation Profile in Human Monocytes

et al. 2019

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Background: Monocyte-derived macrophages are key regulators and producers of reactive oxygen and nitrogen species (ROS/RNS). Pre-clinical and clinical studies suggest that cold physical plasma may be beneficial in the treatment of inflammatory conditions via the release of ROS/RNS. However, it is unknown how plasma treatment affects monocytes and their differentiation profile. Methods: Naïve or phorbol-12-myristate-13-acetate (PMA)-pulsed THP-1 monocytes were exposed to cold physical plasma. The cells were analyzed regarding their metabolic activity as well as flow cytometry (analysis of viability, oxidation, surface marker expression and cytokine secretion) and high content imaging (quantitative analysis of morphology. Results: The plasma treatment affected THP-1 metabolisms, viability, and morphology. Furthermore, a significant modulation CD55, CD69, CD271 surface-expression and increase of inflammatory IL1β, IL6, IL8, and MCP1 secretion was observed upon plasma treatment. Distinct phenotypical changes in THP-1 cells arguing for a differentiation profile were validated in primary monocytes from donor blood. As a functional outcome, plasma-treated monocytes decreased the viability of co-cultured melanoma cells to a greater extent than their non-treated counterparts. Conclusions: Our results suggest plasma-derived ROS/RNS shaped a differentiation profile in human monocytes as evidenced by their increased inflammatory profile (surface marker and cytokines) as well as functional outcome (tumor toxicity).

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“…The results raise its potential as a therapeutic target before and after transplantation. CCL1 has a proinflammatory function and supports Th2 responses [39]. In contrast to CCL15, a mirror image finding is CCL3.…”

Section: Discussionmentioning

confidence: 99%

Circulating chemokine ligand levels before and after successful kidney transplantation

et al. 2016

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BackgroundChemokine ligands (CCLs) play a pivotal role in tissue injury before and after kidney transplantation. Meanwhile, transplantation improves patient’s survival and diminishes morbidity. It is hypothesized, then, that kidney transplantation diminishes pre-transplant (pre-TX) levels of circulating inflammatory CCLs. This retrospective study compared circulating levels and profiles of CCLs before transplantation (pre-TX) and after transplantation (post-TX).MethodsNineteen CCLs (1, 2, 3, 4, 5, 8, 11, 13, 15, 17, 21, 24, 26, 27, CXCL 5, 8, 10, 12 and 13) were measured in 47 stable post-TX recipients, and their stored pre-TX plasma was analyzed by multiplexed fluorescent bead-based immunoassay. Twenty normal controls were included for comparisons. Normalized data was presented as mean ± SD and non-normalized data as median (5–95 % CI). Significance was measured at p < 0.01. Arbitrary upper and lower margins for each CCL at the 95 % CI or 2SD levels in each group were chosen to calculate the percentile of patients in the other group who exceeded these limits. Significant CCL levels present in more than 75 % of patients in a group that exceeded the arbitrary upper or lower set margins in the other two groups were labeled as preferentially characteristic for the respective group.ResultsMore than 75 % of pre- and post-TX patients had levels that exceeded the upper control for CCL1, 11, 15 and CCL15, CCL26 and CXCL13 levels, respectively. More than 75 % of pre- and post-TX patients exceeded the lower control for CCL3, 21, and CCL5 limits, respectively. More than 75 % of post-TX patients demonstrated elevated levels of CCL2, 3, 21, 26 and CXCL13 above the upper pre-TX cut offs. Meanwhile, more than 75 % of post-TX patients exceeded the lower pre-TX levels for CCL1, 4, 5, 8, 13, 15, 17, 24 and CXCL8 and10. Pre-TX was preferentially characterized by elevated CCL1 and 15 and diminished CCL3 and 21. Post-TX was preferentially characterized by elevated CCL26 and CXCL13 and diminished CCL4 and 5.ConclusionEnd stage kidney disease is associated with enhanced circulating inflammatory chemokine levels. Stable kidney transplantation is associated with 1) lowered burden of circulating inflammatory chemokine levels and, 2) elevation in the pro T-helper2 chemokine, CCL26 and the homeostatic CXCL13.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-016-0141-4) contains supplementary material, which is available to authorized users.

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CCR8 Signaling Influences Toll-Like Receptor 4 Responses in Human Macrophages in Inflammatory Diseases

Cited by 20 publications

References 36 publications

Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

Plasma-Derived Reactive Species Shape a Differentiation Profile in Human Monocytes

Circulating chemokine ligand levels before and after successful kidney transplantation

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