THE DIADENOSINE POLYPHOSPHATES AP(3)A AND AP(4)A AND ADENOSINE-TRIPHOSPHATE INTERACT WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR TO DELAY NEUTROPHIL APOPTOSIS - IMPLICATIONS FOR NEUTROPHIL PLATELET INTERACTIONS DURING INFLAMMATION

Incubation of neutrophils with cytokines such as granulocyte macrophag e colony-stimulating factor (GM-CSF) delays their loss of function and changes in cellular morphology that are characteristic of apoptosis. Adenosine triphosphate (ATP) and the diadenosine polyphosphates Ap(4)A and Ap(3)A were almost as effective as GM-CSF in delaying neutrophil apoptosis. The nucleotides could thus preserve cellular morphology, pr otect against chromatin fragmentation, and preserve functions such as NADPH oxidase activity and expression of CD16. Moreover, addition of A TP, Ap(3)A, and Ap(4)A together with GM-CSF resulted in more pronounce d protection from apoptosis than was observed during incubation with e ither the cytokine or the nucleotides alone. Because ATP, Ap(3)A, and Ap(4)A may be secreted from activated platelets, these observations su ggest that platelet-derived products, perhaps acting in combination wi th endothelial-derived or immune cell-derived cytokines, can regulate neutrophil function during certain types of inflammation. (C) 1996 by The American Society of Hematology.