Possible role of H2O2-mediated complement activation and cytokines-mediated fibroblasts superoxide generation on skin inflammation.
The degree of complement activation produced by hydrogen peroxide was estimated by the inhibition of serum homolytic activity (% IHA). Sera from patients with systemic lupus erythematosus and psoriasis vulgaris were resistant to hydrogen-peroxide-mediated complement activation. %IHA negatively correlated with ceruloplasmin level or catalase activity in systemic lupus erythematosus sera, but did not correlate with transferrin level. The addition of free metal ions, FeCl2 or CuCl2, promoted hydrogen-peroxide-mediated complement activation. These results suggest that hydroxyl radical is involved in complement activation and that the factors responsible for the insensitivity of pathological sera to H2O2 are catalase and ceruloplasmin in the sera. Human skin fibroblasts generate superoxide and tumor necrosis factor enhanced it, but interleukin-1 beta inhibited it. Normal serum cultured with fibroblasts for 24 h showed complement activation via catalase-inhibitable process, suggesting that hydrogen peroxide has an important role in fibroblast-mediated complement activation. It is speculated that fibroblasts and complement activation by oxygen radicals have an important role in inflammation and subsequent tissue damage at the site of skin lesion.
Shingu
M
M
Department of Internal Medicine, Kyushu University, Beppu, Japan.
Nonaka
S
S
Nobunaga
M
M
Ahamadzadeh
N
N
D002478:Cells, Cultured; D003167:Complement Activation / Q000187:drug effects*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology; D007375:Interleukin-1 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D011565:Psoriasis / Q000097:blood; D012867:Skin / Q000276:immunology*; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D006861:Hydrogen Peroxide