The effect of 2-deoxyglucose on guinea pig polymorphonuclear leukocyte phagocytosis

Abstract

The effects of 2-deoxyglucose (DOG), an inhibitor of glycolysis, on guinea pig polymorphonuclear leukocytes (PMN) obtained from peritoneal exudates was examined. ATP levels in PMN were reduced by 40% by one hour following an incubation with 2-deoxyglucose. When complement (C3) coated 14C-staphylococcus aureus, C3 coated lipopolysaccharide-paraffin oil droplets (LPS-PO), 14C-pneumococcus opsonized with IgG, or albumin coated paraffin oil droplets opsonized with IgG were added to cell suspensions containing DOG, the phagocytizing rate was 1,310+/-55 cpm/5 X 10(6) cells/15 minutes, 6+/-2 microng paraffin oil (PO)/10(7) cells/minute, 2,250+/-175 cpm/1 X 10(6) cells/20 minutes or 0.037+/-0.01 mg PO/10(7) cells/minute compared to control values of 5,970+/-275 cpm/5 X 10(6) cells/15 minutes, 35+/-3 microng PO/10(7) cells/15 minutes, 4,510+/-200 cpm/1 X 10(6) cells/20 minutes and 0.067+/-0.01 mg PO/10(7) cells/minute. In parallel studies the phagocytic index for latex was 0.74+/-0.28 in DOG compared to control of 2.36+/-1.13 and the phagocytic rate of albumin coated paraffin oil droplets was 0.029+/-0.01 mg PO/10(7) PMN/minute in DOG compared to control of 0.048 mg PO/10(7) cells/minute. When ATP levels were maintained by the simultaneous addition of 5 mM glucose or pyruvate to media containing DOG, latex ingestion was improved to 1.15+/-0.3 with glucose and 1.59+/-0.64 with pyruvate and albumin coated particles to 0.045+/-0.01 mg PO/10(7) PMN/minute with pyruvate. There was no improvement in the uptake of either the C3 dependent particles or IgG coated Pneumococci in media containing DOG and glucose and/or pyruvate. Following the removal of DOG from the extracellular medium and the addition of pyruvate or glucose, phagocytosis of C3 dependent LPS-PO was restored to normal values. Neither the binding of C3 or IgG coated particles to the PMN nor the lateral movement of glycoprotein utilizing concanavalin A capping was affected by DOG. Thus, the presence of DOG in the PMN containing adequate amounts of ATP will selectively and reversibly inhibit those surface events required for phagocytosis of C3 and IgG bound particles but not latex particles or albumin particles which non-specifically bind to PMN.