Do MDL-1+ cells play a broad role in acute inflammation?

Ward, Peter A.

doi:10.1172/jci60122

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…Studies also demonstrated a strong expression of MDL-1 and DAP-12 in mature and differentiated monocytes/macrophages in contrast to undifferentiated bone marrow CD34 + stem cells or monocytes [ 11 ]. Functionally, MDL-1 acts as a signaling receptor for proinflammatory cytokine release [ 12 , 13 ] and is implicated in mediating multiple acute and chronic inflammatory diseases, including hemorrhagic fever, lethal shock, virus-induced brain damage, chronic obstructive pulmonary disease and development of autoimmune arthritis [ 14 – 18 ]. However, the correlation of MDL-1 with atherosclerosis and its behavior are still elusive and remain unknown.…”

Section: Introductionmentioning

confidence: 99%

The macrophage C-type lectin receptor CLEC5A (MDL-1) expression is associated with early plaque progression and promotes macrophage survival

Xiong

Wang

et al. 2017

J Transl Med

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BackgroundBiomarkers of early plaque progression are still elusive. Myeloid DAP12-associating lectin-1 (MDL-1), also called CLEC5A, is a C-type lectin receptor implicated in the progression of multiple acute and chronic inflammatory diseases. However, the relationship between its level and atherosclerosis is unknown. In this study, we aimed to investigate the correlation between macrophage MDL-1 expression and early atherosclerosis progression.MethodsImmunofluorescence staining, real-time PCR and western blot were performed to analyze MDL-1 expression in aorta or mice macrophages. The role of MDL-1 in macrophage survival was further investigated by adenovirus infection and TUNEL assay.ResultsSignificant MDL-1 expression was found in advanced human and apoE−/− mice atherosclerotic plaques, especially in lesional macrophages. In the model of atherosclerosis regression, we found MDL-1 expression was highly downregulated in lesional macrophages from ldlr−/− mouse regressive plaques, coincident with a reduction in lesional macrophage content and marker of M1 proinflammatory macrophages. Furthermore, we found MDL-1 was significantly expressed in inflammatory M1 subtype polarized bone marrow-derived macrophages. In vitro experiments, the level of MDL-1 was remarkably elevated in macrophages treated with pathophysiological drivers of plaque progression, such as oxidized low-density lipoprotein (ox-LDL) and hypoxia. Mechanistically, we demonstrated that MDL-1 overexpression notably promoted macrophage survival and decreased cleaved caspase-3 expression under ox-LDL stimulation, which suggested that it could maintain lesional macrophage survival and cause its accumulation.ConclusionsThis study firstly demonstrated that MDL-1 is mainly expressed in atherosclerotic lesional macrophages and increased macrophage MDL-1 expression is associated with early plaque progression and promotes macrophage survival.Electronic supplementary materialThe online version of this article (10.1186/s12967-017-1336-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

The macrophage C-type lectin receptor CLEC5A (MDL-1) expression is associated with early plaque progression and promotes macrophage survival

Xiong

Wang

et al. 2017

J Transl Med

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“…Activation of CLEC5A by the dengue virus (DENV) results in septic shock mediated by TNF and nitric oxide in mouse models [23,24]. Additionally, monoclonal antibodies against CLEC5A can inhibit plasma leakage and hemorrhagic episodes, and can reduce mortality (16).…”

Section: Introductionmentioning

confidence: 99%

Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects

et al. 2017

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Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR=2.75 and p-value=0.01, OR=2.11 and p-value=0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r=0.55, p=0.008) and TNF production in culture supernatants (Spearman r=0.72, p=0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r=0.67, p=0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors.

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Do MDL-1+ cells play a broad role in acute inflammation?

Cited by 2 publications

References 17 publications

The macrophage C-type lectin receptor CLEC5A (MDL-1) expression is associated with early plaque progression and promotes macrophage survival

The macrophage C-type lectin receptor CLEC5A (MDL-1) expression is associated with early plaque progression and promotes macrophage survival

Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects

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