Thiol-containing compounds inhibit the production of monocyte/macrophage-derived angiogenic activity.
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.
Koch
A E
AE
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Burrows
J C
JC
Polverini
P J
PJ
Cho
M
M
Leibovich
S J
SJ
D000818:Animals; D001681:Biological Assay; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D003470:Culture Media; D004226:Dithioerythritol / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009389:Neovascularization, Pathologic; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D003470:Culture Media; D013438:Sulfhydryl Compounds; D014409:Tumor Necrosis Factor-alpha; D004226:Dithioerythritol; D005978:Glutathione; D004229:Dithiothreitol