ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1375

Synergistic Enhancement Of Aggregated IgG-Induced Tumor Necrosis Factor α In Human Synovial Mast Cells By Interleukin 33

Hyunho Lee1,2, Jun-ichi Kashiwakura3, Masahiko Yanagisawa1,2, Yuki Okamura1,2, Takao Ishii2, Masayuki Seki2, Shu Saito2, Yasuaki Tokuhashi2, Chisei Ra1 and Yoshimichi Okayama1, 1Allergy and Immunology Group, Nihon University School of Medicine, Tokyo, Japan, 2Department of Orthopaedic Surgery, Nihon University School of Medicine, Tokyo, Japan, 3Laboratory for Allergic Disease, RIKEN Center for Integrateive Medical Sciences, Kanagawa, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Recent studies suggest that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). Circulating IgG isotype autoantibodies and synovial immune complexes are detected in RA patients. Therefore a plausible pathway for the activation of synovial MCs is through IgG receptors. However, it has not been well known whether IgG receptors are expressed on human synovial MCs. The purpose of this study was to investigate which IgG receptor(s) on synovial MCs are responsible for MC activation in response to immune complexes (IC), and to evaluate the effect of IL-33, which is believed to play an important role in RA, on IC-induced synovial MC activation.

Methods: We obtained synovial tissue specimens from RA patients and osteoarthritis (OA) patients after total knee replacement surgery. Synovial MCs were enzymatically dispersed. Cultured synovium-derived MCs were generated by culturing synovial cells with stem cell factor, and receptor expression was analyzed using fluorescence-activated cell sorting and immunohistochemical techniques. Mediators released from MCs were measured using enzyme immunoassays or enzymelinked immunosorbent assays.

Results: Primary synovial MCs and cultured synovium-derived MCs obtained from both RA patients and OA patients expressed Fcε receptor I (FcεRI), FcγRI, FcγRII and ST2 but not FcγRIII. Cultured synovium-derived MCs induced degranulation and the production of prostaglandin D2 and tumor necrosis factor α (TNF-α) through FcγRI. The activation through FcγRII caused histamine release from cultured MCs but not from primary MCs. Neutralizing anti-FcγRI monoclonal antibody and anti-FcγRII monoclonal antibody significantly inhibited histamine release induced by aggregated IgG. Aggregated IgG induced TNF-α production (~330 pg/ml/1×106 MCs) from cultured synovium-derived MCs. Although IL-33 did not enhance aggregated IgG-triggered histamine release, IL-33 (30 ng/mL) synergistically enhanced aggregated IgG-induced TNF-α production (~5.2 fold) in cultured synovium-derived MCs.

Conclusion: With Regard to the FcR expression profile, synovial MCs from RA patients and from OA patients were similar. FcγRI was responsible for producing abundant TNF-α from synovial MCs in response to aggregated IgG. Immune complexes may activate synovial MCs through FcγRI and FcγRII. In addition, IL-33 may exacerbate IC-mediated inflammation associated with RA by abundantly producing TNF-α from synovial MCs.

Disclosure:

H. Lee,
None;

J. I. Kashiwakura,
None;

M. Yanagisawa,
None;

Y. Okamura,
None;

T. Ishii,
None;

M. Seki,
None;

S. Saito,
None;

Y. Tokuhashi,
None;

C. Ra,
None;

Y. Okayama,
None.

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