Stimulation of fibroblast proliferation by lactate-mediated oxidants.

Lactate accumulation is a characteristic of wounds in which glycolysis, occurring both aerobically and anaerobically, contributes to its production. Cell proliferation is a critical component of healing wounds, Recently it has been shown that lactate can chelate iron and thus promotes production of hydroxyl radicals. We report here that exogenous lactate increases intracellular oxidants and that the oxidants promote cell growth in cultured dermal fibroblasts in a dose-dependent manner. The production of lactate-mediated oxidant requires iron and hydrogen peroxide and with increasing iron concentration oxidant production is raised as well. However, we found cell proliferation is retarded by 15 mM lactate in the presence of a high iron concentration (7.25 muM). The antioxidants catalase and mannitol abolish the inhibitory effect of high lactate. We conclude from these results that increased proliferation of cultured human fibroblasts by exogenous lactate is mediated by oxidant production.