CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis

Norikuni Kawanaka, Masahiro Yamamura, Tetsushi Aita, Yoshitaka Morita, Akira Okamoto, Masanori Kawashima, Mitsuhiro Iwahashi, Akiko Ueno, Yasukazu Ohmoto, Hirofumi Makino

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

Objective. CD14+,CD16+ monocytes, identified as a minor population of monocytes in human peripheral blood (PB), have been implicated in several inflammatory diseases. We undertook this study to investigate the relevance of this phenotype to joint inflammation in rheumatoid arthritis (RA). Methods. The expression of CD14, CD16, CC chemokine receptor 1 (CCR1), CCR5, and intercellular adhesion molecule 1 (ICAM-1) on monocytes was measured by flow cytometric analysis. Concentrations of the cytokines known to induce CD16 (including transforming growth factor β1 [TGFβ1], macrophage colonystimulating factor [M-CSF], and interleukin-10 [ILl0]) and concentrations of the soluble form of CD14 (sCD14) in plasma and synovial fluid (SF) samples were measured by enzyme-linked immunosorbent assay. The induction of CD16 on RA blood monocytes cultured for 18 hours with 1 or with all 3 cytokines was determined. Results. The mean ± SD frequency of CD14+,CD16+ blood monocytes was significantly increased in RA patients (11.7 ± 5.6%; n = 105) compared with healthy controls (9.5 ± 2.2%; n = 15) (P < 0.01), and the patient group with an increased frequency of CD16+ monocytes (≥13.9%) had active disease, as defined by increased counts of tender and swollen joints, levels of acute-phase reactants, and titers of rheumatoid factor. The response to drug therapy correlated with changes in the frequency of this phenotype. The expression of CD16 on SF monocytes from RA patients was markedly elevated compared with the expression on PB monocytes. CD16 expression on RA blood monocytes was augmented in vitro by IL-10, M-CSF, and TGFβ1. Plasma concentrations of these cytokines and of sCD14 were significantly higher in RA patients with high CD16+ monocyte frequencies than in those with low CD16+ monocyte frequencies or in healthy controls. CD14+,CD16+ monocytes expressed higher levels of CCR1, CCR5, and ICAM-1 than did regular CD14++,CD16-monocytes, particularly in active RA. Conclusion. These results indicate that the maturation of blood monocytes into tissue-infiltrative CD16+ cells before entry into the joint, induced by cytokine spillover from the inflamed joint, may contribute to the persistent joint inflammation of RA.

Original languageEnglish
Pages (from-to)2578-2586
Number of pages9
JournalArthritis and Rheumatism
Volume46
Issue number10
DOIs
Publication statusPublished - Oct 1 2002

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Monocytes
Rheumatoid Arthritis
Joints
Inflammation
CCR1 Receptors
Cytokines
Synovial Fluid
Transforming Growth Factors
Intercellular Adhesion Molecule-1
Interleukin-10
Macrophages
Phenotype
Acute-Phase Proteins
Rheumatoid Factor
Enzyme-Linked Immunosorbent Assay
Drug Therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Kawanaka, N., Yamamura, M., Aita, T., Morita, Y., Okamoto, A., Kawashima, M., ... Makino, H. (2002). CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis. Arthritis and Rheumatism, 46(10), 2578-2586. https://doi.org/10.1002/art.10545

CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis. / Kawanaka, Norikuni; Yamamura, Masahiro; Aita, Tetsushi; Morita, Yoshitaka; Okamoto, Akira; Kawashima, Masanori; Iwahashi, Mitsuhiro; Ueno, Akiko; Ohmoto, Yasukazu; Makino, Hirofumi.

In: Arthritis and Rheumatism, Vol. 46, No. 10, 01.10.2002, p. 2578-2586.

Research output: Contribution to journalArticle

Kawanaka, N, Yamamura, M, Aita, T, Morita, Y, Okamoto, A, Kawashima, M, Iwahashi, M, Ueno, A, Ohmoto, Y & Makino, H 2002, 'CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis', Arthritis and Rheumatism, vol. 46, no. 10, pp. 2578-2586. https://doi.org/10.1002/art.10545
Kawanaka N, Yamamura M, Aita T, Morita Y, Okamoto A, Kawashima M et al. CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis. Arthritis and Rheumatism. 2002 Oct 1;46(10):2578-2586. https://doi.org/10.1002/art.10545
Kawanaka, Norikuni ; Yamamura, Masahiro ; Aita, Tetsushi ; Morita, Yoshitaka ; Okamoto, Akira ; Kawashima, Masanori ; Iwahashi, Mitsuhiro ; Ueno, Akiko ; Ohmoto, Yasukazu ; Makino, Hirofumi. / CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis. In: Arthritis and Rheumatism. 2002 ; Vol. 46, No. 10. pp. 2578-2586.
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abstract = "Objective. CD14+,CD16+ monocytes, identified as a minor population of monocytes in human peripheral blood (PB), have been implicated in several inflammatory diseases. We undertook this study to investigate the relevance of this phenotype to joint inflammation in rheumatoid arthritis (RA). Methods. The expression of CD14, CD16, CC chemokine receptor 1 (CCR1), CCR5, and intercellular adhesion molecule 1 (ICAM-1) on monocytes was measured by flow cytometric analysis. Concentrations of the cytokines known to induce CD16 (including transforming growth factor β1 [TGFβ1], macrophage colonystimulating factor [M-CSF], and interleukin-10 [ILl0]) and concentrations of the soluble form of CD14 (sCD14) in plasma and synovial fluid (SF) samples were measured by enzyme-linked immunosorbent assay. The induction of CD16 on RA blood monocytes cultured for 18 hours with 1 or with all 3 cytokines was determined. Results. The mean ± SD frequency of CD14+,CD16+ blood monocytes was significantly increased in RA patients (11.7 ± 5.6{\%}; n = 105) compared with healthy controls (9.5 ± 2.2{\%}; n = 15) (P < 0.01), and the patient group with an increased frequency of CD16+ monocytes (≥13.9{\%}) had active disease, as defined by increased counts of tender and swollen joints, levels of acute-phase reactants, and titers of rheumatoid factor. The response to drug therapy correlated with changes in the frequency of this phenotype. The expression of CD16 on SF monocytes from RA patients was markedly elevated compared with the expression on PB monocytes. CD16 expression on RA blood monocytes was augmented in vitro by IL-10, M-CSF, and TGFβ1. Plasma concentrations of these cytokines and of sCD14 were significantly higher in RA patients with high CD16+ monocyte frequencies than in those with low CD16+ monocyte frequencies or in healthy controls. CD14+,CD16+ monocytes expressed higher levels of CCR1, CCR5, and ICAM-1 than did regular CD14++,CD16-monocytes, particularly in active RA. Conclusion. These results indicate that the maturation of blood monocytes into tissue-infiltrative CD16+ cells before entry into the joint, induced by cytokine spillover from the inflamed joint, may contribute to the persistent joint inflammation of RA.",
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AU - Yamamura, Masahiro

AU - Aita, Tetsushi

AU - Morita, Yoshitaka

AU - Okamoto, Akira

AU - Kawashima, Masanori

AU - Iwahashi, Mitsuhiro

AU - Ueno, Akiko

AU - Ohmoto, Yasukazu

AU - Makino, Hirofumi

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N2 - Objective. CD14+,CD16+ monocytes, identified as a minor population of monocytes in human peripheral blood (PB), have been implicated in several inflammatory diseases. We undertook this study to investigate the relevance of this phenotype to joint inflammation in rheumatoid arthritis (RA). Methods. The expression of CD14, CD16, CC chemokine receptor 1 (CCR1), CCR5, and intercellular adhesion molecule 1 (ICAM-1) on monocytes was measured by flow cytometric analysis. Concentrations of the cytokines known to induce CD16 (including transforming growth factor β1 [TGFβ1], macrophage colonystimulating factor [M-CSF], and interleukin-10 [ILl0]) and concentrations of the soluble form of CD14 (sCD14) in plasma and synovial fluid (SF) samples were measured by enzyme-linked immunosorbent assay. The induction of CD16 on RA blood monocytes cultured for 18 hours with 1 or with all 3 cytokines was determined. Results. The mean ± SD frequency of CD14+,CD16+ blood monocytes was significantly increased in RA patients (11.7 ± 5.6%; n = 105) compared with healthy controls (9.5 ± 2.2%; n = 15) (P < 0.01), and the patient group with an increased frequency of CD16+ monocytes (≥13.9%) had active disease, as defined by increased counts of tender and swollen joints, levels of acute-phase reactants, and titers of rheumatoid factor. The response to drug therapy correlated with changes in the frequency of this phenotype. The expression of CD16 on SF monocytes from RA patients was markedly elevated compared with the expression on PB monocytes. CD16 expression on RA blood monocytes was augmented in vitro by IL-10, M-CSF, and TGFβ1. Plasma concentrations of these cytokines and of sCD14 were significantly higher in RA patients with high CD16+ monocyte frequencies than in those with low CD16+ monocyte frequencies or in healthy controls. CD14+,CD16+ monocytes expressed higher levels of CCR1, CCR5, and ICAM-1 than did regular CD14++,CD16-monocytes, particularly in active RA. Conclusion. These results indicate that the maturation of blood monocytes into tissue-infiltrative CD16+ cells before entry into the joint, induced by cytokine spillover from the inflamed joint, may contribute to the persistent joint inflammation of RA.

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