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CD16 (FcRgammaIII) as a potential marker of osteoclast precursors in psoriatic arthritis.

Chiu YG, Shao T, Feng C, Mensah KA, Thullen M, Schwarz EM, Ritchlin CT - Arthritis Res. Ther. (2010)

Bottom Line: Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation.An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis.Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Allergy/Immunology & Rheumatology Unit, University of Rochester Medical School, 601 Elmwood Avenue, Rochester, NY 14642, USA. grace_chiu@urmc.rochester.edu

ABSTRACT

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterized by bone erosion mediated by osteoclasts (OC). Our previous studies showed an elevated frequency of OC precursors (OCP) in PsA patients. Here, we examined if OC arise from CD16-positive monocytes in PsA.

Methods: Peripheral blood mononuclear cells (PBMC) or monocytes were isolated from human peripheral blood and sorted based on CD16 expression. Sorted cells were cultured alone or with bone wafers in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Enumeration and bone erosion activity of OC were examined after culture. The effects of tumor necrosis factor-alpha (TNFalpha), OC-promoting (M-CSF plus RANKL), and dendritic cell (DC)-promoting (GM-CSF plus interleukin (IL)-4) cytokines on CD16 surface expression were examined by flow cytometry.

Results: PsA and psoriasis (Ps) subjects had a higher percentage of circulating inflammatory CD14+CD16+ cells than healthy controls (HC). Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation. PBMC of Ps and PsA had a higher frequency of cells expressing intermediate levels of CD16. OC were mainly derived from CD16+ cells in PsA. Increased CD16 expression was associated with a higher bone erosion activity in PsA.

Conclusions: An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis. Intriguingly, TNFalpha blocked CD16 expression on a subset of CD14+ monocytes. Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.

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Ps and PsA patients have a higher percentage of CD14+CD16+ cells. Human peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood, stained with an antibody cocktail composed of CD14-APC, CD16-PE, 7AAD, and analyzed by flow cytometry. Dead cells were excluded by 7AAD+. (a) Classical (CD14+CD16-, red line) and non-classical (CD14+CD16+, blue line) monocytes were labeled based on the classification by Strauss-Ayali and colleagues [5]. (b) The percentage of CD14+CD16+ cells in the PBMC of 16 healthy controls (HC), and 29 psoriasis (Ps), 28 psoriatic arthritis (PsA), and 8 rheumatoid arthritis (RA) patients. (c) The percentage of CD14+CD16+ cells in enriched human monocytes from HC and PsA. Monocytes were enriched by the Human Monocyte Enrichment Cocktail. The percentage of CD14+CD16+ cells in enriched monocytes from HC (2.6 ± 1.6%) and PsA patients (10.3 ± 9.5%) are shown in [a] and [b], respectively. The data are representative of 10 independent experiments.
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Figure 1: Ps and PsA patients have a higher percentage of CD14+CD16+ cells. Human peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood, stained with an antibody cocktail composed of CD14-APC, CD16-PE, 7AAD, and analyzed by flow cytometry. Dead cells were excluded by 7AAD+. (a) Classical (CD14+CD16-, red line) and non-classical (CD14+CD16+, blue line) monocytes were labeled based on the classification by Strauss-Ayali and colleagues [5]. (b) The percentage of CD14+CD16+ cells in the PBMC of 16 healthy controls (HC), and 29 psoriasis (Ps), 28 psoriatic arthritis (PsA), and 8 rheumatoid arthritis (RA) patients. (c) The percentage of CD14+CD16+ cells in enriched human monocytes from HC and PsA. Monocytes were enriched by the Human Monocyte Enrichment Cocktail. The percentage of CD14+CD16+ cells in enriched monocytes from HC (2.6 ± 1.6%) and PsA patients (10.3 ± 9.5%) are shown in [a] and [b], respectively. The data are representative of 10 independent experiments.

Mentions: One-way analysis of variance with Tukey's post hoc multiple comparison test was used to compare four different groups in Figure 1(b) and Table 1. The two-sample t-test was used for comparison of two groups with continuous data. The significance level was set at 0.05. The Satterthwaite two-sample test was used to analyze data presented in Figure 1(c). The Fisher's exact test was used to analyze the frequencies of CD16 expression presented in Table 1. All statistical analyses were performed on SAS 9.1 (SAS Institute Inc., Cary, NC, USA).


CD16 (FcRgammaIII) as a potential marker of osteoclast precursors in psoriatic arthritis.

Chiu YG, Shao T, Feng C, Mensah KA, Thullen M, Schwarz EM, Ritchlin CT - Arthritis Res. Ther. (2010)

Ps and PsA patients have a higher percentage of CD14+CD16+ cells. Human peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood, stained with an antibody cocktail composed of CD14-APC, CD16-PE, 7AAD, and analyzed by flow cytometry. Dead cells were excluded by 7AAD+. (a) Classical (CD14+CD16-, red line) and non-classical (CD14+CD16+, blue line) monocytes were labeled based on the classification by Strauss-Ayali and colleagues [5]. (b) The percentage of CD14+CD16+ cells in the PBMC of 16 healthy controls (HC), and 29 psoriasis (Ps), 28 psoriatic arthritis (PsA), and 8 rheumatoid arthritis (RA) patients. (c) The percentage of CD14+CD16+ cells in enriched human monocytes from HC and PsA. Monocytes were enriched by the Human Monocyte Enrichment Cocktail. The percentage of CD14+CD16+ cells in enriched monocytes from HC (2.6 ± 1.6%) and PsA patients (10.3 ± 9.5%) are shown in [a] and [b], respectively. The data are representative of 10 independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875642&req=5

Figure 1: Ps and PsA patients have a higher percentage of CD14+CD16+ cells. Human peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood, stained with an antibody cocktail composed of CD14-APC, CD16-PE, 7AAD, and analyzed by flow cytometry. Dead cells were excluded by 7AAD+. (a) Classical (CD14+CD16-, red line) and non-classical (CD14+CD16+, blue line) monocytes were labeled based on the classification by Strauss-Ayali and colleagues [5]. (b) The percentage of CD14+CD16+ cells in the PBMC of 16 healthy controls (HC), and 29 psoriasis (Ps), 28 psoriatic arthritis (PsA), and 8 rheumatoid arthritis (RA) patients. (c) The percentage of CD14+CD16+ cells in enriched human monocytes from HC and PsA. Monocytes were enriched by the Human Monocyte Enrichment Cocktail. The percentage of CD14+CD16+ cells in enriched monocytes from HC (2.6 ± 1.6%) and PsA patients (10.3 ± 9.5%) are shown in [a] and [b], respectively. The data are representative of 10 independent experiments.
Mentions: One-way analysis of variance with Tukey's post hoc multiple comparison test was used to compare four different groups in Figure 1(b) and Table 1. The two-sample t-test was used for comparison of two groups with continuous data. The significance level was set at 0.05. The Satterthwaite two-sample test was used to analyze data presented in Figure 1(c). The Fisher's exact test was used to analyze the frequencies of CD16 expression presented in Table 1. All statistical analyses were performed on SAS 9.1 (SAS Institute Inc., Cary, NC, USA).

Bottom Line: Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation.An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis.Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Allergy/Immunology & Rheumatology Unit, University of Rochester Medical School, 601 Elmwood Avenue, Rochester, NY 14642, USA. grace_chiu@urmc.rochester.edu

ABSTRACT

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterized by bone erosion mediated by osteoclasts (OC). Our previous studies showed an elevated frequency of OC precursors (OCP) in PsA patients. Here, we examined if OC arise from CD16-positive monocytes in PsA.

Methods: Peripheral blood mononuclear cells (PBMC) or monocytes were isolated from human peripheral blood and sorted based on CD16 expression. Sorted cells were cultured alone or with bone wafers in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Enumeration and bone erosion activity of OC were examined after culture. The effects of tumor necrosis factor-alpha (TNFalpha), OC-promoting (M-CSF plus RANKL), and dendritic cell (DC)-promoting (GM-CSF plus interleukin (IL)-4) cytokines on CD16 surface expression were examined by flow cytometry.

Results: PsA and psoriasis (Ps) subjects had a higher percentage of circulating inflammatory CD14+CD16+ cells than healthy controls (HC). Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation. PBMC of Ps and PsA had a higher frequency of cells expressing intermediate levels of CD16. OC were mainly derived from CD16+ cells in PsA. Increased CD16 expression was associated with a higher bone erosion activity in PsA.

Conclusions: An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis. Intriguingly, TNFalpha blocked CD16 expression on a subset of CD14+ monocytes. Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.

Show MeSH
Related in: MedlinePlus