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Production of soluble ICAM-1 by mononuclear cells from patients with rheumatoid arthritis patients
M Shingu1, M Hashimoto, M Nobunaga
1Department of Clinical Immunology, Kyushu University, Beppu, Japan.
Abstract:
The present study was designed to quantify the level of the soluble form of ICAM-1 (sICAM-1) produced by mononuclear cells (MNC) of rheumatoid arthritis (RA) patients, and to correlate these levels with the disease activity and with the amounts of cytokines or rheumatoid factors (RF) produced by MNC. Unstimulated synovial fluid (SF) MNC produced higher amounts of sICAM-1 than peripheral blood (PB) MNC in RA patients (P < 0.01). sICAM-1 production by PHA-stimulated MNC was higher in RA SF MNC than RA or normal PB MNC (P < 0.01). The amounts of SICAM-1 produced correlated with the amounts of soluble IL-2 receptor produced (P < 0.02) but not with IL-1B or the Lansbury activity index in RA PB MNC. sICAM-1 correlated with the amounts of soluble CD23 and IL-4 produced by normal PB MNC (P < 0.01). The amounts of sICAM-1 correlated with IgG-RF (P < 0.02) and IgM-RF (P < 0.01) produced by unstimulated MNC obtained from the bone marrow (BM) of RA patients. ICAM-1 expression of T-lymphocyte subsets, B lymphocytes, and monocytes obtained from RA PB and RA BM assayed by two-color flow cytometry ranged from 0.1 to 6%, which was not appreciably different from that of normal controls. The monocyte fraction of RA PB MNC produced significantly higher amounts of sICAM-1 than lymphocyte fraction. These results suggest that sICAM-1 produced by MNC may be a marker of cell activation in T and B lymphocytes, in contrast to the transient increase of ICAM-1 expression.
Insights
Soluble ICAM-1 (sICAM-1) levels are elevated in mononuclear cells (MNC) from rheumatoid arthritis (RA) patients, particularly in synovial fluid. sICAM-1 production correlates with disease markers and cell activation in RA.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Rheumatoid arthritis (RA) is a chronic inflammatory disease.
- Intercellular Adhesion Molecule-1 (ICAM-1) plays a role in immune cell trafficking and activation.
- The soluble form of ICAM-1 (sICAM-1) may serve as a biomarker in inflammatory conditions.
Purpose of the Study:
- To quantify sICAM-1 production by mononuclear cells (MNC) in RA patients.
- To correlate sICAM-1 levels with disease activity, cytokines, and rheumatoid factors (RF).
- To investigate sICAM-1 as a potential marker of cell activation.
Main Methods:
- Quantification of sICAM-1 in synovial fluid (SF) and peripheral blood (PB) MNC from RA patients.
- Stimulation of MNC with PHA to assess sICAM-1 production.
- Flow cytometry to measure ICAM-1 expression on lymphocyte and monocyte subsets.
- Correlation analysis with cytokines (IL-2 receptor, IL-1B, IL-4), RF, and disease activity index.
Main Results:
- RA SF MNC produced significantly higher sICAM-1 than RA PB MNC.
- PHA-stimulated MNC showed higher sICAM-1 production in RA SF MNC compared to RA or normal PB MNC.
- sICAM-1 levels correlated with soluble IL-2 receptor, soluble CD23, IL-4, IgG-RF, and IgM-RF.
- Monocyte fraction of RA PB MNC produced more sICAM-1 than lymphocytes.
- ICAM-1 expression on cell subsets was not significantly different from controls.
Conclusions:
- Elevated sICAM-1 production by MNC, especially in SF, suggests its involvement in RA pathogenesis.
- sICAM-1 may serve as a marker of T and B lymphocyte activation in RA.
- Correlation with RF and cytokines supports sICAM-1's role in immune response within RA.