Deficiency in immune complex uptake by chronic granulomatous disease neutrophils

Receptor-mediated binding and endocytosis by normal and chronic granulomatous disease (CGD) polymorphonuclear (PMN) leucocytes have been investigated. Our results suggest that activation of the respiratory burst is a requisite for normal immune complex internalization. Cell-associated immune complexes were detected by fluorescence microscopy, electron microscopy and flow cytometric techniques. These measurements indicate that immune complex uptake is defective in CGD patients, but not in normal subjects. Antibody-dependent binding and complement-dependent binding and endocytosis were not affected. The functional association of the respiratory burst and antibody-dependent endocytosis was further explored using rhodamine-labelled glucose oxidase:anti-glucose oxidase immune complexes. These complexes generate H2O2 in the presence of glucose. When treated with these complexes, CGD PMNs showed similar glucose-dose-dependent increases in both H2O2 production and cell-associated fluorescence. Therefore: (1) respiratory burst and immune complex uptake are coexisting deficiencies that may be a manifestation of a single defect; and (2) the respiratory burst may be one participant in immune complex endocytic triggering.