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 qu antities 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 func tion as novel modulators of cell function. For this report we have mea sured the effects of the diadenosine polyphosphates Ap(5)A and Ap(6)A on neutrophil apoptosis. These molecules can themselves delay neutroph il apoptosis (as assessed by morphology, function, CD16 expression and chromatin integrity), and are as effective on a molar basis as ATP, A p(3)A and Ap(4)A. Moreover, these dinucleotides act synergistically wi th granulocyte-macrophage colony-stimulating factor (GM-CSF) to delay neutrophil apoptosis. Thus, diadenosine polyphosphates may act, in con cert with cytokines, as novel modulators of neutrophil function and su rvival in certain types of inflammatory conditions.