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

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Abstract

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 cuture systems from the bone marrow of a CGD patient with those from normal subjects. The cells of normal colony-forming 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 functional characteristics of CGD are embedded in the genetic program of granulocyte progenitors.

Authors

P E Newburger, M S Kruskall, J M Rappeport, S H Robinson, M E Chovaniec, H J Cohen