Calcium signalling is altered in myeloid cells with a deficiency in NADPH oxidase activity.

SUMMARY The relation of O₂ ^.- -production and Ca²⁺ homeostasis was investigated in PLB-985 cell lines and neutrophilic granulocytes from peripheral blood. In differentiated wild-type PLB-985 cells, a high level of O₂ ^.- -production was associated with a significant decrease in the membrane potential and the inhibition of capacitative Ca²⁺ entry. These correlations were not observed in gp91^{phox –/–} cells or in cells transfected with a non-functional mutant of gp91^phox (Thr341Lys). Membrane depolarization and inhibition of Ca²⁺ entry reappeared in cells transfected with wild-type gp91^phox . These experiments demonstrate that inhibition of Ca²⁺ entry depends on the presence of a functional NADPH oxidase. The Ca²⁺ signal induced by stimulation of chemotactic receptors also showed remarkable differences: [Ca²⁺ ]_ic in the sustained phase was higher in gp91^phox–/– than in wild-type cells. Alteration of the Ca²⁺ signal was reproduced by treating peripheral blood neutrophils with the NADPH oxidase inhibitor diphenylene-iodonium. It is concluded that the deficiency in O₂ ^.- -production is accompanied by significant alterations of Ca²⁺ homeostasis in myeloid cells. [ABSTRACT FROM AUTHOR]