The effect of organic acids on phytohaemagglutinin-activated proliferation of human lymphocytes in vitro.
The present study assesses the effects of 25 organic acids on in vitro proliferation of human peripheral lymphocyte stimulated with phytohaemagglutinin (PHA). Lymphocytes were cultured in flat-bottomed 96-well microplates at 37 degrees C for 96 h in the presence of the mitogen and of one acid. The concentrations of organic acids tested in the cultures were from 1 to 5 mM, corresponding to those usually found in the blood of patients with organic acidaemias. Cellular growth was measured by the incorporation of 6[3H]-thymidine into cellular DNA. We observed that tiglic (2-methylcrotonic), alpha-keto-beta-methylvaleric, aminoadipic, sebacic and alpha-ketoisocaproic acids strongly inhibited lymphocyte DNA synthesis, whereas alpha-ketoisovaleric, propionic, alpha-hydroxy-beta-methylvaleric, alpha-methylbutyric and isobutyric acids moderately suppressed DNA synthesis. Lactic and ethylmalonic acids, however, stimulated DNA synthesis. The most inhibitory acids were added to cultures at different times after the beginning of the incubation period. Except for tiglic acid, whose action persisted even after 48 h from the onset of cultures, the others acted only when added during the first 24 h. The present study demonstrated that organic acids modulate DNA synthesis in mitogen-stimulated human lymphocytes.
Schlottfeldt
J
J
Departamento de Bioquimica, UFRGS Unidade de Genetica Medica, Porto Alegre, Brazil.
Blazina
L R
LR
Wannmacher
C M
CM
Wajner
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D002469:Cell Separation; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D003998:Dicarboxylic Acids; D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D004247:DNA