NEUTROPHILS AND MONOCYTES FROM SUBJECTS WITH THE MEDITERRANEAN G6PD VARIANT - EFFECT OF PLASMODIUM-FALCIPARUM HEMOZOIN ON G6PD ACTIVITY, OXIDATIVE BURST AND CYTOKINE PRODUCTION

Glucose 6-phosphate dehydrogenase (G6PD) activity and oxidative burst were measured in neutrophils and monocytes from five, hemizygous, G6PD -deficient (Mediterranean variant) individuals and five normal control s. Additionally, tumor necrosis factor (TNF), interleukin-10 (IL-10), interleukin-12 (IL-12) release and phagocytosis of the malarial pigmen t hemozoin or opsonized erythrocytes (RBC) were measured in monocytes recovered from G6PD-deficient and normal individuals. G6PD activity wa s significantly lower in ''deficient monocytes'' (38% residual activit y, p = 0.01) and not significantly different in ''deficient neutrophil s'' (79% residual activity, p = 0.83) compared to homologous leukocyte s recovered from normal controls. Oxidative burst was not significantl y different in ''deficient'' versus ''normal'' neutrophils and monocyt es, Previous phagocytosis of hemozoin decreased the phorbol ester indu ced oxidative burst in ''deficient'' and ''normal'' monocytes but not in neutrophils. Phagocytosis of hemozoin and RBC strongly stimulated c ytokine production. With the exception of IL-10, the cytokine producti on pattern was comparable in ''deficient'' versus ''normal'' cells. In cubation with high concentrations of hemozoin (equivalent to 300 RBC p er monocyte) strongly stimulated TNF production. Lipopolysaccharide (L PS) had an additive effect on TNF production induced by hemozoin or op sonized RBC, IL-12 production was induced only by the presence of larg e amounts of hemozoin, IL-10 production was increased in normal monocy tes incubated with RBC or hemozoin, LPS increased IL-10 production sig nificantly in monocytes incubated with RBC or low amounts of hemozoin (equivalent to 30 RBC per monocyte), but had no effect when given alon e or in conjunction with high concentrations of hemozoin, Interestingl y, deficient monocytes produced less IL-10 than normal cells under the se conditions. In conclusion, except for IL-10 production, we did not find major functional differences between neutrophils and monocytes fr om individuals with or without the Mediterranean G6PD mutation.