Effect of deuterium oxide on leukotriene C4 generation in immunologically stimulated human leukocytes

Addition of deuterium oxide (D2O), 6-36%, resulted in a dose-dependent increase in allergen- or anti-IgE-induced leukotriene C4 (LTC4) generation from human basophils. In the presence of 36% D2O, the enhancement was 260 +/- 135% for allergen stimulation and 480 +/- 152% for anti-IgE stimulation as compared with the control incubated in normal buffer. The increasing effect of D2O on LTC4 generation from basophils was completely reversed by washing the cells before incubation with allergen. Vinblastine as well as colchicine, at a concentration of 100 microM, counteracted the effect of D2O. The enhanced release of histamine and LTC4 from basophils challenged with allergen was suppressed by Dimaprit, a histamine H2 receptor agonist, at a concentration required to inhibit the release by 50% of 5 X 10(-5) M for histamine and 10(-5) M for LTC4. These observations suggest that microtubules may be involved in LTC4 generation from immunologically stimulated basophils.