Expression of hypoxia‐inducible factor 1α by macrophages in the rheumatoid synovium: implications for targeting of therapeutic genes to the inflamed joint
AP Hollander, KP Corke, AJ Freemont… - Arthritis & Rheumatism …, 2001 - Wiley Online Library
Arthritis & Rheumatism: Official Journal of the American College …, 2001•Wiley Online Library
Objective To determine if the rheumatoid synovium is a suitable target for hypoxia‐regulated
gene therapy. Methods Sequential sections of wax‐embedded synovial membrane samples
were obtained from 10 patients with rheumatoid arthritis (RA), 10 with primary osteoarthritis
(OA), and from 6 healthy controls. Membrane sections from each patient were
immunostained for hypoxia‐inducible factor 1α (HIF‐1α) and CD68 (a pan–macrophage
marker). Results HIF‐1α was expressed abundantly by macrophages in most rheumatoid …
gene therapy. Methods Sequential sections of wax‐embedded synovial membrane samples
were obtained from 10 patients with rheumatoid arthritis (RA), 10 with primary osteoarthritis
(OA), and from 6 healthy controls. Membrane sections from each patient were
immunostained for hypoxia‐inducible factor 1α (HIF‐1α) and CD68 (a pan–macrophage
marker). Results HIF‐1α was expressed abundantly by macrophages in most rheumatoid …
Objective
To determine if the rheumatoid synovium is a suitable target for hypoxia‐regulated gene therapy.
Methods
Sequential sections of wax‐embedded synovial membrane samples were obtained from 10 patients with rheumatoid arthritis (RA), 10 with primary osteoarthritis (OA), and from 6 healthy controls. Membrane sections from each patient were immunostained for hypoxia‐inducible factor 1α (HIF‐1α) and CD68 (a pan–macrophage marker).
Results
HIF‐1α was expressed abundantly by macrophages in most rheumatoid synovia, predominantly close to the intimal layer but also in the subintimal zone. There was markedly lower expression of HIF‐1α in OA synovia, and it was absent from all of the healthy synovia.
Conclusion
These observations indicate that macrophages transduced with a therapeutic gene under the control of a hypoxia‐inducible promoter could be administered to RA patients systemically. Migration of these cells to synovial tissue would result in the transgene being switched on in diseased joints but not in healthy tissues.
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