The diadenosine polyphosphates Ap3A and Ap4A 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 macrophage 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 Ap4A and AP3A were almost as effective as GM-CSF in delaying neutrophil apoptosis. The nucleotides could thus preserve cellular morphology, protect against chromatin fragmentation, and preserve functions such as NADPH oxidase activity and expression of CD16. Moreover, addition of ATP, AP3A and AP4A together with GM-CSF resulted in more pronounced protection from apoptosis than was observed during incubation with either the cytokine or the nucleotides alone. Because ATP, Ap3A, and AP4A may be secreted from activated platelets, these observations suggest that platelet-derived products, perhaps acting in combination with endothelial-derived or immune cell-derived cytokines, can regulate neutrophil function during certain types of inflammation.
Gasmi
L
L
Cellular and Metabolic Regulation Group, Department of Biochemistry, University of Liverpool, UK.
McLennan
A G
AG
Edwards
S W
SW
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D001792:Blood Platelets / Q000502:physiology*; D002843:Chromatin / Q000648:ultrastructure; D003864:Depression, Chemical; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D015539:Platelet Activation; D017452:Receptors, IgG / Q000032:analysis
D015415:Biomarkers; D002843:Chromatin; D015226:Dinucleoside Phosphates; D017452:Receptors, IgG; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000255:Adenosine Triphosphate; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases