Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils.
Pregnancy is associated with changes in host susceptibility to infections and inflammatory disease. We hypothesize that metabolic enzyme trafficking affects maternal neutrophil activation. Specifically, immunofluorescence microscopy has shown that glucose-6-phosphate dehydrogenase (G-6-PDase), the rate-controlling step of the hexose monophosphate shunt (HMS), is located near the cell periphery in control neutrophils but is found near the microtubule-organizing centers in cells from pregnant women. Cytochemical studies confirmed that the distribution of the G-6-PDase antigen is coincident with functional G-6-PDase activity. Metabolic oscillations within activated pregnancy neutrophils are higher in amplitude, though lower in frequency, than activated control neutrophils, suggesting limited HMS activity. Analysis of radioisotope-labeled carbon flux from glucose to CO(2) indicates that the HMS is intact in leukocytes from pregnant women, but its level is not enhanced by cell stimulation. Using extracellular fluorescent markers, activated pregnancy neutrophils were found to release reactive oxygen metabolites (ROMs) at a lower rate than activated control neutrophils. However, basal levels of ROM production in polarized pregnancy neutrophils were greater than in control neutrophils. Microtubule-disrupting agents reversed the observed changes in G-6-PDase trafficking, metabolic oscillations, and ROM production by maternal neutrophils. G-6-PDase trafficking appears to be one mechanism regulating ROM production by maternal neutrophils.
Kindzelskii
Andrei L
AL
Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, USA.
Huang
Ji-Biao
JB
Chaiworapongsa
Tinnakorn
T
Fahmy
Ryan M
RM
Kim
Yeon Mee
YM
Romero
Roberto
R
Petty
Howard R
HR
D000818:Animals; D018385:Centrosome / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D004198:Disease Susceptibility / Q000276:immunology / Q000378:metabolism; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007239:Infections / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009249:NADP / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism*; D011247:Pregnancy / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D008070:Lipopolysaccharides; D019384:Nucleic Acid Synthesis Inhibitors; D016877:Oxidants; D017382:Reactive Oxygen Species; D015638:Cytochalasin D; D009249:NADP; D007371:Interferon-gamma; D005954:Glucosephosphate Dehydrogenase; D003078:Colchicine