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.
Perlman, Harris 1; Nguyen, Nadine 1; Liu, Hongtao 1; Eslick, Joy 2; Esser, Sybille 3; Walsh, Kenneth 3; Moore, Terry L. 2; Pope, Richard M. 1
[Article] Arthritis & Rheumatism. 48(11):3096-3101, November 2003.

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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.

(C) 2003, American College of Rheumatology