Production of oxygen radicals by fibroblasts and neutrophils from a patient with x-linked chronic granulomatous disease.
Recently, a superoxide-generating NADPH-oxidase system in human fibroblasts has been described. Therefore, we reassessed the possible use of this cell type for prenatal diagnosis of CGD patients comparing normal and CGD peripheral blood neutrophils (PMN) and skin fibroblasts in their reactive oxygen intermediate (ROI)-producing capacity. While PMN of the CGD patient showed a clearly reduced respiratory burst activity, which correlated well with the measured content of cytochrome b558, fibroblasts of the same individual showed no impaired production of superoxide anion or H2O2 upon stimulation by cytokines (TNF and IL-1) or other agents (Ca2+ ionophores and PAF, unpublished results). Furthermore, fibroblasts of the CGD patient or of normal donors could be inhibited in ROI production by diphenylene iodonium (DPI) and 2-iodobiphenyl. In contrast to PMN, no inhibition of the fibroblast NADPH-oxidase system was observed using staurosporin, an inhibitor of proteinkinase C. These data demonstrate, in contrast to previous studies, that fibroblasts are able to produce ROI. Nevertheless, since fibroblasts obtained from a CGD patient exhibited no difference in ROI production compared with fibroblasts obtained from healthy donors, they are not suitable for prenatal diagnosis of CGD.
Emmendörffer
A
A
Dept. of Immunobiology, Fraunhofer Institute, Hannover, Germany.
Roesler
J
J
Elsner
J
J
Raeder
E
E
Lohmann-Matthes
M L
ML
Meier
B
B
D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D003573:Cytochrome b Group / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D012016:Reference Values; D012867:Skin / Q000378:metabolism*; D013481:Superoxides / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014960:X Chromosome
D003573:Cytochrome b Group; D007375:Interleukin-1; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D000001:Calcimycin; C036888:cytochrome b558; D019255:NADPH Oxidases