Dataset Information

CD14+ Cells with the Phenotype of Infiltrated Monocytes Consist of Distinct Populations Characterized by Anti-inflammatory as well as Pro-inflammatory Activity in Gouty Arthritis.

ABSTRACT: It has been suggested that inflammasome-mediated IL-1? production in monocytic cells is responsible for the acute inflammatory response in gouty arthritis. However, phenotypical and functional analyses of monocytes during gouty arthritis have yet to be conducted. Therefore, we investigated the characteristics of monocytes/macrophages in the synovial fluid cells of patients with acute gout. The number and frequency of monocytes/macrophages in the synovial fluid mononuclear cells (SFMCs) of patients was examined. The expression of markers for monocyte recruitment and tissue-resident macrophages, the production of pro-inflammatory and anti-inflammatory cytokines, and phagocytosis were analyzed in the monocytes/macrophages of patients with acute gout attacks. The number and frequency of CD14+CD3-CD19-CD56- monocytes/macrophages was markedly increased in the SFMCs of patients with gout compared to those of patients with rheumatoid arthritis (RA). CD14+ cells showed the phenotypes of infiltrated monocytes rather than tissue-resident macrophages, characterized by a high expression of CCR2, MRP8, and MRP14, but a low expression of MERTK and 25F9. These cells had the capacity to produce pro-inflammatory cytokines such as TNF-? and IL-1? after stimulation with lipopolysaccharides. In addition, anti-inflammatory features, including CD163 expression and IL-10 production from CD14+ cells, were significantly higher in patients with gout than in those with RA. CD14+ cells with phenotype of M2 macrophages had high phagocytic activity for monosodium urate crystals. Thus, our results indicate that monocytes/macrophages from patients with gout have the phenotype of infiltrated monocytes, and these cells consist of different populations characterized by anti-inflammatory activities as well as pro-inflammatory functions.

SUBMITTER: Jeong JH

PROVIDER: S-EPMC5635328 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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CD14<sup>+</sup> Cells with the Phenotype of Infiltrated Monocytes Consist of Distinct Populations Characterized by Anti-inflammatory as well as Pro-inflammatory Activity in Gouty Arthritis.

Jeong Ji Hye JH Hong Seokchan S Kwon Oh Chan OC Ghang Byeongzu B Hwang Inseok I Kim Yong-Gil YG Lee Chang-Keun CK Yoo Bin B

Frontiers in immunology 20171006

It has been suggested that inflammasome-mediated IL-1β production in monocytic cells is responsible for the acute inflammatory response in gouty arthritis. However, phenotypical and functional analyses of monocytes during gouty arthritis have yet to be conducted. Therefore, we investigated the characteristics of monocytes/macrophages in the synovial fluid cells of patients with acute gout. The number and frequency of monocytes/macrophages in the synovial fluid mononuclear cells (SFMCs) of patien ...[more]

PMID: 29056937

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Project description:BackgroundSystemic sclerosis (SSc) is an autoimmune disease characterized by overproduction of extracellular matrix (ECM) and multiorgan fibrosis. Animal studies pointed to bone marrow-derived cells as a potential source of pathological ECM-producing cells in immunofibrotic disorders. So far, involvement of monocytes and macrophages in the fibrogenesis of SSc remains poorly understood.Methods and resultsImmunohistochemistry analysis showed accumulation of CD14+ monocytes in the collagen-rich areas, as well as increased amount of alpha smooth muscle actin (αSMA)-positive fibroblasts, CD68+ and mannose-R+ macrophages in the heart and lungs of SSc patients. The full genome transcriptomics analyses of CD14+ blood monocytes revealed dysregulation in cytoskeleton rearrangement, ECM remodeling, including elevated FN1 (gene encoding fibronectin) expression and TGF-β signalling pathway in SSc patients. In addition, single cell RNA sequencing analysis of tissue-resident CD14+ pulmonary macrophages demonstrated activated profibrotic signature with the elevated FN1 expression in SSc patients with interstitial lung disease. Peripheral blood CD14+ monocytes obtained from either healthy subjects or SSc patients exposed to profibrotic treatment with profibrotic cytokines TGF-β, IL-4, IL-10, and IL-13 increased production of type I collagen, fibronectin, and αSMA. In addition, CD14+ monocytes co-cultured with dermal fibroblasts obtained from SSc patients or healthy individuals acquired a spindle shape and further enhanced production of profibrotic markers. Pharmacological blockade of the TGF-β signalling pathway with SD208 (TGF-β receptor type I inhibitor), SIS3 (Smad3 inhibitor) or (5Z)-7-oxozeaenol (TGF-β-activated kinase 1 inhibitor) ameliorated fibronectin levels and type I collagen secretion.ConclusionsOur findings identified activated profibrotic signature with elevated production of profibrotic fibronectin in CD14+ monocytes and CD14+ pulmonary macrophages in SSc and highlighted the capability of CD14+ monocytes to acquire a profibrotic phenotype. Taking together, tissue-infiltrating CD14+ monocytes/macrophages can be considered as ECM producers in SSc pathogenesis.

Project description:BackgroundEvidence on the changes in the absolute counts of monocyte subpopulations in sepsis is missing.MethodsFirstly, absolute counts of circulating CD14pos/HLA-DRpos/CD45pos monocytes were measured by flow cytometry in 70 patients with Gram-negative sepsis and in 10 healthy volunteers. In the second phase, immunophenotyping was performed and the absolute count of circulating inflammatory monocytes and of circulating CD14dim/CD16pos/CD45pos patrolling monocytes were measured in another 55 patients and 10 healthy volunteers. Measurements were repeated on days 3, 7, and 10. Results were correlated with survival after 28 days.ResultsGreater numbers of CD14pos/HLA-DRpos/CD45pos monocytes were found on day 1 in survivors compared to nonsurvivors (p = 0.030). Receiver operating characteristic (ROC) analysis showed that a cutoff higher than 337 cells/mm3 on day 1 could discriminate between survivors and nonsurvivors with a positive predictive value (PPV) of 91.1%. Logistic regression including Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE) II score showed that an absolute count greater than 337 cells/mm3 was independently associated with unfavorable outcome (odds ratio (OR) 0.19, p = 0.050). The absolute counts of inflammatory and of CD14dim/CD16pos/CD45pos monocytes were greater in patients than healthy controls during the entire 10 days of follow-up. The absolute counts on day 3 of CD14dim/CD16pos/CD45pos monocytes were greater in survivors than nonsurvivors (p = 0.027). ROC analysis revealed that the cutoff at 27 cells/mm3 could discriminate between survivors and nonsurvivors with PPV of 94.1%. Logistic regression including age, SOFA score, and APACHE II score showed that an absolute count greater than 27 cells/mm3 was independently associated with unfavorable outcome (OR 0.06, p = 0.033). Logistic regression analysis showed that intra-abdominal infection on day 1 was predictive of low CD14dim/ CD16pos/CD45pos count on day 3.ConclusionCirculating counts of inflammatory and patrolling monocytes are greatly increased in Gram-negative sepsis. Absolute counts of CD14pos/HLA-DRpos/CD45pos monocytes on day 1 and CD14dim/CD16pos/CD45pos monocytes on day 3 are independently associated with final outcome.Trial registrationClinicalTrials.gov, NCT01223690 . Registered retrospectively on 18 October 2010.

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Dataset Information

CD14+ Cells with the Phenotype of Infiltrated Monocytes Consist of Distinct Populations Characterized by Anti-inflammatory as well as Pro-inflammatory Activity in Gouty Arthritis.

Publications

CD14<sup>+</sup> Cells with the Phenotype of Infiltrated Monocytes Consist of Distinct Populations Characterized by Anti-inflammatory as well as Pro-inflammatory Activity in Gouty Arthritis.

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