Enhancement of normal neutrophil chemiluminescence by chronic granulomatous disease neutrophils

Neutrophils and other phagocytic cells from patients with chronic granulomatous disease (CGD) lack the ability to generate reactive oxygen intermediates (ROI), although other phagocytic functions appear to be intact. The effects of CGD neutrophils on the ability of normal neutrophils to produce ROI as measured by luminol-enhanced chemiluminescence (CL) were examined. Normal neutrophils (2×10⁵) had a peak CL response to phorbol myristate acetate (PMA; 20 ng/ml) of 6.5±0.9 mV, while the CL response of CGD neutrophils was completely absent. However, the addition of CGD neutrophils (8×10⁵) to normal neutrophils (2×10⁵) markedly increased the peak CL response to PMA to 11.0+-1.1 mV (P < 0.001). The peak response of normal neutrophils (2×10⁵) alone to the peptideN-formyl-methionyl-leucyl-phenylalanine (FMLP; 10^–6 M) was 9.0±1.1mV, and this increased to 22.2±3.5 mV (P < 0.001) when 8×10⁵ CGD neutrophils were added and to 18.9±3.6 mV (P<0.005) when 4×10⁵ CGD neutrophils were added. Thus, CGD neutrophils increase the release of ROI from normal cells, suggesting nonoxidative regulatory factors in ROI production.This work was supported in part by grants GI517-02 and 0008-08 from the Cystic Fibrosis Foundation and HD-09800 and AI-15332 from the National Institutes of Health.