Neutrophil apoptosis is delayed by the diadenosine polyphosphates, Ap(5)A and Ap(6)A: Synergism with granulocyte-macrophage colony-stimulating factor

In addition to ATP, platelets and other cell types can secrete high quantities of diadenosine polyphosphates Ap(3)A, Ap(4)A, Ap(5)A and Ap(6)A. There is increasing evidence to show that these molecules can function as novel modulators of cell function. For this report we have measured the effects of the diadenosine polyphosphates Ap(5)A and Ap(6)A on neutrophil apoptosis. These molecules can themselves delay neutrophil apoptosis (as assessed by morphology, function, CD16 expression and chromatin integrity), and are as effective on a molar basis as ATP, Ap(3)A and Ap(4)A. Moreover, these dinucleotides act synergistically with granulocyte-macrophage colony-stimulating factor (GM-CSF) to delay neutrophil apoptosis. Thus, diadenosine polyphosphates may act, in concert with cytokines, as novel modulators of neutrophil function and survival in certain types of inflammatory conditions.