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 controls. Additionally, tumor necrosis factor (TNF), interleukin-10 (IL-10), interleukin-12 (IL-12) release and phagocytosis of the malarial pigment hemozoin or opsonized erythrocytes (RBC) were measured in monocytes recovered from G6PD-deficient and normal individuals. G6PD activity was significantly lower in "deficient monocytes" (38% residual activity, p = 0.01) and not significantly different in "deficient neutrophils" (79% residual activity, p = 0.83) compared to homologous leukocytes recovered from normal controls. Oxidative burst was not significantly different in "deficient" versus "normal" neutrophils and monocytes. Previous phagocytosis of hemozoin decreased the phorbol ester induced oxidative burst in "deficient" and "normal" monocytes but not in neutrophils. Phagocytosis of hemozoin and RBC strongly stimulated cytokine production. With the exception of IL-10, the cytokine production pattern was comparable in "deficient" versus "normal" cells. Incubation with high concentrations of hemozoin (equivalent to 300 RBC per monocyte) strongly stimulated TNF production. Lipopolysaccharide (LPS) had an additive effect on TNF production induced by hemozoin or opsonized RBC. IL-12 production was induced only by the presence of large amounts of hemozoin. IL-10 production was increased in normal monocytes incubated with RBC or hemozoin. LPS increased IL-10 production significantly in monocytes incubated with RBC or low amounts of hemozoin (equivalent to 30 RBC per monocyte), but had no effect when given alone or in conjunction with high concentrations of hemozoin. Interestingly, deficient monocytes produced less IL-10 than normal cells under these conditions. In conclusion, except for IL-10 production, we did not find major functional differences between neutrophils and monocytes from individuals with or without the Mediterranean G6PD mutation.
Mordmüller
B
B
Sektion Humanparasitologie, Institut für Tropenmedizin, Universität Tübingen, Germany. benjamin.mordmueller@uni-tuebingen.de
Turrini
F
F
Long
H
H
Kremsner
P G
PG
Arese
P
P
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004912:Erythrocytes / Q000502:physiology; D014644:Genetic Variation; D005954:Glucosephosphate Dehydrogenase / Q000097:blood* / Q000187:drug effects / Q000235:genetics*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood* / Q000201:enzymology*; D006420:Hemeproteins / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D019083:Mediterranean Region; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010587:Phagocytosis; D010860:Pigments, Biological / Q000494:pharmacology; D010963:Plasmodium falciparum; D012016:Reference Values; D016897:Respiratory Burst / Q000187:drug effects*
D016207:Cytokines; D006420:Hemeproteins; D008070:Lipopolysaccharides; D010860:Pigments, Biological; D016753:Interleukin-10; D018664:Interleukin-12; C020753:hemozoin; D005954:Glucosephosphate Dehydrogenase