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Thiol-containing compounds inhibit the production of monocyte/macrophage-derived angiogenic activity
A E Koch1, J C Burrows, P J Polverini
1Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Abstract:
Macrophage (M phi)-mediated angiogenesis is believed to play an important role in the pathogenesis of rheumatoid arthritis. Gold sodium thiomalate, which is used in the treatment of rheumatoid arthritis, is a potent inhibitor of the production of m phi-derived angiogenic activity. To determine the mechanism of this inhibition, we studied the effects of thiol containing compounds (TCCs) on elicited mouse peritoneal m phi and lipopolysaccharide stimulated normal human monocytes. Monocyte/m phi conditioned media were potently angiogenic when assayed in rat corneas, while conditioned media from viable monocyte/m phi s treated with TCCs (at concentrations of 8.3-16.6 x 10(-5) M) were not. TCCs inhibited production of angiogenic activity by the m phi s rather than affecting other components of the angiogenic response such as the angiogenic factors or the target microvasculature of the rat cornea. Levels of the angiogenic mediator tumor necrosis factor-alpha (TNF-alpha) were not decreased in conditioned media of monocyte/m phi s treated with TCCs. We conclude that TCCs are potent inhibitors of the production of m phi-mediated angiogenic activity. This action of TCCs on m phi s may be in part responsible for the mechanism of action of therapeutic gold compounds in rheumatoid arthritis.
Insights
Thiol-containing compounds (TCCs) inhibit macrophage-mediated angiogenesis, a key factor in rheumatoid arthritis. This finding offers insight into how gold compounds treat rheumatoid arthritis by affecting macrophage activity.
Area of Science:
- Immunology
- Rheumatology
- Biochemistry
Background:
- Macrophage (M phi)-mediated angiogenesis is crucial in rheumatoid arthritis pathogenesis.
- Gold sodium thiomalate, a rheumatoid arthritis therapeutic, inhibits M phi-derived angiogenic activity.
Purpose of the Study:
- To elucidate the mechanism by which thiol-containing compounds (TCCs) inhibit M phi-mediated angiogenesis.
- To investigate the effect of TCCs on M phi and human monocyte-derived angiogenic activity.
Main Methods:
- Assessing the angiogenic potential of monocyte/M phi conditioned media in rat corneas.
- Treating elicited mouse peritoneal M phi and lipopolysaccharide-stimulated human monocytes with TCCs.
- Measuring tumor necrosis factor-alpha (TNF-alpha) levels in conditioned media.
Main Results:
- TCCs significantly inhibited the production of M phi-derived angiogenic activity.
- TCCs did not affect existing angiogenic factors or the rat cornea's microvasculature.
- Tumor necrosis factor-alpha (TNF-alpha) levels remained unchanged, indicating TCCs target production, not specific mediators.
Conclusions:
- Thiol-containing compounds (TCCs) are potent inhibitors of macrophage-mediated angiogenic activity production.
- This inhibitory action on macrophages may contribute to the therapeutic mechanism of gold compounds in rheumatoid arthritis.