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 fibrob lasts has been described. Therefore, we reassessed the possible use of this cell type for prenatal diagnosis of CGD patients comparing norma l and CGD peripheral blood neutrophils (PMN) and skin fibroblasts in t heir 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 b(558) , fibroblasts of the same individual showed no impaired production of superoxide anion or H2O2 upon stimulation by cytokines (TNF and IL-l) or other agents (Ca2+ ionophores and PAF, unpublished results). Furthe rmore, fibroblasts of the CGD patient or of normal donors could be inh ibited in ROI production by diphenylene iodonium (DPI) and 2-iodobiphe nyl 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 fibro blasts are able to produce ROI. Nevertheless, since fibroblasts obtain ed from a CGD patient exhibited no difference in ROI production compar ed with fibroblasts obtained from healthy donors, they are not suitabl e for prenatal diagnosis of CGD.