Activation of serum complement leads to inhibition of ascorbic acid transport.
Ascorbic acid is transported into 3T6 fibroblasts by a carrier-mediated, energy-dependent saturable active process with a Km of 112 microM and Vmax of 158 pmole/min/mg protein. The transport is dependent on extracellular Na+ concentration which reduces the Km. It was recently observed in this laboratory that bovine serum contained a heat-labile factor which, after interaction with bacterial endotoxin (lipopolysaccharides), inhibited ascorbic acid transport (J.J. Alleo and H. Padh, Proc Soc Exp Biol Med 179:128-131, 1985). We report here that the inhibition of ascorbic acid transport by endotoxin is mediated by the activation of serum complement. This was done by examining the activation of complement by other activators like zymosan and immunocomplexes (e.g., albumin and antibodies to albumin). Ascorbate transport was inhibited by the mixture of unheated serum and the activators. No inhibition was observed with serum devoid of C3 (component 3 of the complement). When C3-deficient serum was reconstituted by the addition of purified C3, the endotoxin-induced inhibition of ascorbate transport was restored. The implication of these findings is that in spite of a normal intake and blood level of the vitamin, tissues may not be getting adequate vitamin C during disease states when the complement in serum is activated. In other words, what may be considered an adequate intake of vitamin C under health conditions may not be adequate under disease conditions.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D001205:Ascorbic Acid / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D003167:Complement Activation; D003176:Complement C3 / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D051379:Mice; D009751:Nutritional Requirements
D000936:Antigen-Antibody Complex; D003176:Complement C3; D004731:Endotoxins; D001205:Ascorbic Acid