The role of lactic acid in autocrine B-cell growth stimulation.
Growth and survival of Epstein-Barr virus (EBV)-immortalized B lymphocytes cultured at low cell densities require autocrine soluble factors. In this study, we have purified a low molecular weight autocrine soluble factor that promotes growth of EBV-immortalized B cells in serum-free conditions and identified it as lactic acid (LA). Synthetic LA stimulated growth in EBV-immortalized B cells at 1-10 mM, a concentration of LA measured in the culture supernatant of EBV-immortalized cell lines. LA alone was found to account for greater than 70% of the autocrine growth factor activity in serum-free supernatants of EBV-immortalized B cells. Aminooxyacetate, a glutamate-oxaloacetate transaminase inhibitor, specifically inhibited B-cell growth induced by LA, suggesting that this process requires mitochondrial-cytosol transfers. Thus, LA is an autocrine stimulatory molecule that in serum-free conditions is essential for the continuous proliferation of EBV-immortalized B cells. This represents an unexpected function for LA.
Pike
S E
SE
Laboratory of Immunology, Food and Drug Administration, Bethesda, MD 20892.
Markey
S P
SP
Ijames
C
C
Jones
K D
KD
Tosato
G
G
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D002851:Chromatography, High Pressure Liquid; D006133:Growth Substances / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000235:genetics; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid
D006133:Growth Substances; D015850:Interleukin-6; D007773:Lactates; D019344:Lactic Acid