Generation and Role of Active oxygens in Cells

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1. For characterizing superoxide-generating system of phagocytes, we analyzed the cells of the patients with chronic granulomatous disease (CGD), because their genetic backgrounds have apparently well understood. The system is composed of 4 components, namely gp91-phox, p22-phox, p47-phox, and p67-phox. The former two make a cytochrome b558 lying on the membrane of phagocytes. In a patient, a common genetic phenotype has been noted to prevail over all kinds of his phagocytes. We, however, have discovered a 62-year male patient whose granulocyte fraction definitely contain a small population with normal amount of surface cytochrome b558. The population has been identified as eosinophils. Neither gp91-phox nor phorbol ester-stimulated chemiluminescence (CL) response are observed in his neutrophils and monocytes. His eosinophils definitely contain gp91-phox and exhibit the normal extent of CL response. Molecular analyzes have shown that coding sequences of his gp91-phox mRNA and its gene, and the poly (A) signal of the gene are normal. We have discovered a point mutation in the 5'-flanking region of his gp91-phox gene and are now extensively characterizing the function of that mutated region.2. For characterizing superoxide-generating system of non-phagocytic cells, we used B lymphocytes, fibroblasts, mesangial cells, and others. The system of B lymphocytes is essential' the same as that of phagocytes. The expression of gp91-phox in B lymphocytes should be the same as that of neutrophils and monocytes but not of eosinophils. The amount of cytochrome b558 in B lymphocytes is quite low comparing to that of granulocytes, which corresponds to low CL response of the lymphocytes. Fibroblasts may have a different cytochrome because the cells of the patient with CGD normally generate superoxide anions. The superoxide-generating system of non-phagocytic cells should be hereafter reexamined by using molecular probes prepared for phagocytic cells.