Studies on the mechanism of platelet-activating factor production in GM-CSF primed neutrophils: involvement of protein synthesis and phospholipase A2 activation.
GM-CSF regulates the growth of hemopoietic progenitor cells, enhances the responsiveness of mature PMN and primes these cells for synthesis of leukotrienes and PAF in response to secondary stimuli. The biochemical requirements for PAF production in GM-CSF primed PMN was examined using different metabolic inhibitors. GM-CSF stimulates uridine incorporation into RNA and inhibitors for RNA and protein synthesis decrease PAF synthesis in our model. This suggests a role for gene expression and de novo synthesis of proteins in the action of GM-CSF. Different PLA2 inhibitors, including a 9 amino-acid peptide derived from a conserved region of the calpactin superfamily, decrease PAF production, indicating that in GM-CSF primed PMN the chemotactic peptide fMLP triggers lipid mediator synthesis by activating PLA2.
Wirthmueller
U
U
Institute of Clinical Immunology, Inselspital, Bern, Switzerland.
de Weck
A L
AL
Dahinden
C A
CA
D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis*; D001091:Arachidonate Lipoxygenases / Q000096:biosynthesis*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007930:Leucine / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D010972:Platelet Activating Factor; D003609:Dactinomycin; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide; D001091:Arachidonate Lipoxygenases; D001094:Arachidonate 5-Lipoxygenase; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D007930:Leucine; D014529:Uridine