Acetaldehyde-modified serum proteins inhibit mitogen-stimulated human lymphocyte transformation

Sera obtained from healthy volunteers immediately before and 8 h after the rapid consumption of 1.2 g ethanol/kg body weight were dialysed against RPMI 1640 and added ab initio to microcultures of normal human lymphocytes containing 1-3 micrograms phytohaemagglutinin (PHA)/ml or 2-8 micrograms pokeweed mitogen (PWM)/ml. When compared with the pre-alcohol sera, the post-alcohol sera inhibited lymphocyte transformation after 48 h incubation with either mitogen. In other experiments, acetaldehyde-albumin complexes were generated by reacting solutions of human serum albumin with 45-720 microM acetaldehyde, and the same quantity of either unmodified albumin or acetaldehyde-modified albumin was included in freshly-prepared lymphocyte microcultures containing 3 micrograms PHA/ml or 8 micrograms PWM/ml. When compared with unmodified albumin, acetaldehyde-modified albumin inhibited lymphocyte transformation after 48 h of culture with either mitogen. The inhibition of lymphocyte transformation caused by post-alcohol sera and acetaldehyde-modified albumin was partially corrected after treatment of the proteins with 1.55 mM sodium borohydride at a pH of 9.5. The data indicate that post-alcohol sera contain a non-dialysable activity which inhibits mitogen-stimulated lymphocyte transformation in vitro and that at least part of this activity may reside in acetaldehyde-modified serum albumin.