Early changes in cyclic AMP and calcium efflux during phagocytosis by neutrophils from normals and patients with chronic granulomatous disease.
During phagocytosis of serum-treated zymosan particles (STZ) human neutrophils respond within 5 sec by a two-fold increase in cAMP concomitantly with an increase in 45Ca-efflux from intracellular stores. The changes in cyclic AMP and calcium efflux during phagocytosis were essentially the same whether the cells were preincubated in the presence of 5 mM glucose or without glucose. However, the phagocytic capacity, and oxygen consumption and degranulation during phagocytosis were reduced about 20%-25% in the absence of glucose. Addition of 2-deoxyglucose and iodoacetamide, which results in depletion of cellular ATP, abolished the cAMP increments during phagocytosis and profoundly inhibited calcium efflux. At the same time, the phagocytic capacity and STZ-induced oxygen consumption and degranulation were severely impaired. The mitochondrial inhibitors, cyanide, azide, and antimycin A, in the presence of glucose, did not affect the cellular ATP levels. Neither were cAMP increments and calcium effluxes during phagocytosis affected by these drugs, and likewise these did not affect phagocytosis or the post-phagocytic events. Neutrophils from two patients with X-linked chronic granulomatous disease (CGD) and one patient with the autosomal recessive form elicited normal increases in cAMP levels and calcium effluxes after addition of STZ despite no increase in oxygen consumption showing that these early metabolic events are not affected by the lack of oxidase function.
D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D000963:Antimetabolites / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000097:blood*; D005947:Glucose / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000378:metabolism*; D010101:Oxygen Consumption; D010587:Phagocytosis; D013997:Time Factors
D000963:Antimetabolites; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium