Rheumatoid arthritis synovial fluid macrophages express decreased tumor necrosis factor-related apoptosis-inducing ligand R2 and increased decoy receptor tumor necrosis factor-related apoptosis-inducing ligand R3.

Abstract

OBJECTIVE:

To characterize the expression pattern of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its cognate receptors (TRAIL R1, R2, R3, and R4) on rheumatoid arthritis (RA) synovial fluid (SF) lymphocytes and monocyte/macrophages and on cultured RA synovial fibroblasts.

METHODS:

The expression of TRAIL and TRAIL receptors on RA SF lymphocytes and monocyte/macrophages, normal macrophages, and RA synovial fibroblasts was examined by flow cytometry with previously characterized monoclonal antibodies. The ability of adenoviral-mediated delivery of TRAIL to induce macrophage or RA synovial fibroblast apoptosis was examined by flow cytometry.

RESULTS:

By flow cytometry, neither TRAIL nor its cognate receptors was detectable on RA SF lymphocytes or RA synovial fibroblasts. In contrast, RA SF macrophages expressed TRAIL R3, a decoy receptor (P < 0.01 versus isotype control), but not TRAIL, or TRAIL R1, R2, or R4. Normal peripheral blood-derived monocyte-differentiated macrophages expressed TRAIL R2 (P < 0.01), but not TRAIL or the other TRAIL receptors. Adenoviral-mediated delivery of TRAIL had no effect on the survival of normal macrophages or RA synovial fibroblasts but readily induced apoptosis in the prostate cancer cell line (PC-3) that expressed TRAIL R1 and R2.

CONCLUSION:

TRAIL R1 and R2, which are required for signal transmission by TRAIL, were not detected on RA SF lymphocytes, macrophages, or synovial fibroblasts. These observations do not support a potential therapeutic role for TRAIL in RA.

• Authors: Harris Perlman, Nadine Nguyen, Hongtao Liu, Joy Eslick, Sybille Esser, Kenneth Walsh, Terry L Moore, Richard M Pope
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 48 Issue 11 Pg. 3096-101 (Nov 2003) ISSN: 0004-3591 [Print] United States
• PMID: 14613271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Apoptosis Regulatory Proteins
• Membrane Glycoproteins
• Receptors, Cell Surface
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Member 6b
• TNF-Related Apoptosis-Inducing Ligand
• TNFRSF6B protein, human
• TNFSF10 protein, human
• Tumor Necrosis Factor-alpha

Topics

• Adenoviridae Infections
• Apoptosis
• Apoptosis Regulatory Proteins
• Arthritis, Rheumatoid (metabolism, pathology)
• Cell Line, Tumor
• Flow Cytometry
• Humans
• Macrophages (metabolism, pathology, virology)
• Membrane Glycoproteins (metabolism)
• Receptors, Cell Surface (metabolism)
• Receptors, Tumor Necrosis Factor (metabolism)
• Receptors, Tumor Necrosis Factor, Member 6b
• Synovial Fluid (cytology, metabolism)
• Synovial Membrane (metabolism, pathology)
• TNF-Related Apoptosis-Inducing Ligand
• Transfection
• Tumor Necrosis Factor-alpha (metabolism)