Chronic granulomatous disease. Expression of the metabolic defect by in vitro culture of bone marrow progenitors.

Abstract

A B S T R A C T Chronic granulomatous disease (CGD), an often fatal syndrome of recurrent infections, results from the inability of patients' peripheral blood phagocytic leukocytes to generate superoxide despite otherwise normal phagocytic functions such as ingestion and degranulation. Circulating granulocytes and monocytes are the progeny of bone marrow progenitor cells, colony-forming units in culture. We compared the function of cells grown in two different in vitro culture systems from the bone marrow of a CGD patient with those from normal subjects. The cells ofnormal colonyforming unit in culture colonies grown in semisolid medium reduced nitroblue tetrazolium dye when stimulated by phorbol myristate acetate; none of the cells from colonies derived from CGD marrow did so. Cells grown in liquid suspension culture from normal marrow generated superoxide nearly as well as normal peripheral blood granulocytes; those from CGD marrow produced no superoxide. Similarly cultured cells from both normal and CGD marrow ingested opsonized bacteria at rates equal to peripheral blood granulocytes. CGD marrow-derived cells showed increased exocytic degranulation relative to both normal marrow-derived cells and normal peripheral blood granulocytes. These studies demonstrate that the basic

Decrease in CuZn‐superoxide dismutase mRNA level during differentiation of human monocytic and promyelotic leukemia cells

“…On the other hand, myeloperoxidase activity is reported to be less in mature granulocytes than in immature HL-60 cells [29]. Differentiated U937 or HL-60 cells produce active oxygens [9,30], and the authors initially expected that CuZn-SOD mRNA would increase during differentiation as a protective measure against the cytotoxic effects of active oxygens. The a ±, standard deviation from triplicate assays decrease in CuZn-SOD mRNA followed by that of its activity, as observed in the present communication, may be biologically significant for the efficient production of active oxygens.…”

“…The expression of the proto-oncogene c-myc is diminished during the differentiation of HL-60 or U937 cells [4][5][6][7], whereas that of c-sis and c-fms genes increases during TPA-induced differentiation [8]. Besides these phenotypic changes, differentiated HL-60 and U937 cells produce superoxide anions [9].…”

Characterization and Sequencing of a Respiratory Burst-inhibiting Acid Phosphatase from Francisella tularensis

“…Measurement of Respiratory Burst in Neutrophils-Respiratory burst activity of isolated porcine neutrophils was measured in the presence and absence of AcpA by following the production of superoxide using modifications of a previously described method (16). Briefly, the superoxide dismutase-inhibitable reduction of ferricytochrome c at 550 nm was continuously measured at 37°C using either a Beckman DU-50 spectrophotometer or an Aminco dual-beam recording spectrophotom-eter (DW 2000).…”

Adenovirus-mediated gene transfer into monocyte-derived macrophages of patients with X-linked chronic granulomatous disease: ex vivo correction of deficient respiratory burst

“…3 More than 60% of patients already show the phenotypic characteristics of CGD patients suffer from a chromosome X-linked the disease. 10 Therefore, CD34 + peripheral blood hematoinherited subtype of the disease (X-CGD). X-CGD is poietic progenitor cells are of particular interest, as this caused by deficient or non-functional gp91…”