Concanavalin A as a probe for studying the mechanism of metabolic stimulation of leukocytes.
The disruption of the molecular organization of the plasma membrane of leukocytes by phagocytosable particles, or by agents such as surfactants, antibodies, phospholipase C, fatty acids and chemotactic factors, leads to a stimulation of the phagocyte oxidative metabolism. Concanavalin A (Con A) has been used as a tool to study the mechanism of this metabolic regulation. The binding of Con A to the surface of polymorphonuclear leukocytes (PMNL) or macrophages produces a rapid enhancement of oxygen uptake and glucose oxidation through the hexose monophosphate pathway (HMP). This is explained by an activation of the granular NADPH oxidase, the key enzyme in the metabolic stimulation. The effect of Con A is not due to endocytosed lectin, since Con A covalently coupled to large sepharose beads still acts as stimulant. The metabolic changes caused by Con A are reversible. If, after the onset of stimulation, sugars with high affinity for Con A are added to the leukocyte suspension, the activity of granular NADPH oxidase and the rate of respiration and glucose oxidation return to their resting values. The metabolic burst, while partially supressed by treatment of PMNL with iodoacetate, sodium flouride and cytochalasin B, is slightly increased by colchicine. Con A induces a selective release of granular enzymes (beta-glucuronidase, peroxidase, alkaline phosphatase) from PMNL, whereas no leakage of cytoplasmic enzymes is observed. The enzyme release is inhibited by iodoacetate and by drugs known to increase cell levels of cyclic AMP. Based on a current view of the mode of interaction between Con A and cell surfaces, a model of the metabolic disruption of leukocytes is presented.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D003208:Concanavalin A / Q000378:metabolism; D003486:Cyanides / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010587:Phagocytosis; D011048:Polarography; D013268:Stimulation, Chemical
D003486:Cyanides; D003208:Concanavalin A; D000242:Cyclic AMP; D005947:Glucose