UTILIZATION OF LIPOSOMES FOR CORRECTION OF THE METABOLIC DEFICIENCIES IN CHRONIC GRANULOMATOUS DISEASE (CGD)

Abstract

Previous studies have shown that latex particles coated with glucose oxidase (GO) would partially correct the metabolic defects in CGD polymorphonuclear leukocytes (PMN). In order to develop a technique with better therapeutic advantage, we studied the efficacy of preparing liposomes (LP) containing the hydrogen peroxide (H2O2) generating GO. The activity of GO incorporated within the LP could only be demonstrated after treatment of the LP with Triton X-100. LP were coated with heat-aggregated human IgG, thereby increasing their capability to be phagocytized by PMN. CGD PMN oxidized glucose-l-14C upon phagocytosis of GO-containing LP at levels 4-fold greater at 30 min than CGD PMN stimulated either with latex particles or with heat-inactivated Go-containing LP. Similarly, CGD PMN increased their iodination activity 4-fold over 60 min upon exposure to GO-containing LP when compared to only a 1.3-fold increase upon exposure to heat-inactivated GO-containing LP plus zymosan. After 100 min of incubation with Staphylococcus aureus and GO-containing, LP CGD PMN killed 0.6 log bacteria compared to a 0.3 log bacteria kill with heat-inactivated GO-containing LP. We conclude that GO can be incorporated into LP and these LP can be internalized by CGD to generate H2O2. Thus, a potential therapeutic modality for CGD may be the administration of LP containing oxidant generating enzymes.

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Ismail, G., Boxer, L. & Baehner, R. UTILIZATION OF LIPOSOMES FOR CORRECTION OF THE METABOLIC DEFICIENCIES IN CHRONIC GRANULOMATOUS DISEASE (CGD). Pediatr Res 11, 501 (1977). https://doi.org/10.1203/00006450-197704000-00789

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