Binding of arachidonic acid to myeloid-related proteins (S100A8/A9) enhances phagocytic NADPH oxidase activation.
Activation of the O(2)(-) generating NADPH oxidase of phagocytes results from the assembly of the membrane-bound flavocytochrome b(558) with cytosolic proteins, p67(phox), p47(phox), and Rac. However, it has been recently reported that the arachidonic acid- and calcium-binding heterodimer S100A8/A9, abundant in neutrophil cytosol, influences the activation process. In a semi-recombinant system comprising neutrophil membranes, recombinant proteins, p67(phox), p47(phox), GTPgamma S-loaded Rac2, and arachidonic acid (AA), both the rate and the extent of the oxidase activation were increased by S100A8/A9, provided it was preloaded with AA. Binding of [(14)C]AA to S100A8/A9 was potentiated by recombinant cytosolic phox proteins and GTPgammaS, suggesting the formation of a complex, comprising oxidase activating proteins and S100A8/A9, with a greater affinity for AA. The rate constant of oxidase activation was not increased by AA-loaded S100A8/A9, whereas the maximal oxidase activity elicited was twice as high. AA-loaded S100A8/A9 increases oxidase activation probably by decreasing the deactivation rate.
Bouzidi
Farid
F
Laboratoire de Biochimie et Biophysique des Systèmes Intégrés (UMR 5092 CEA-CNRS-UJF), Département Réponse et Dynamique Cellulaires, CEA-Grenoble, France.
Doussiere
Jacques
J
D016718:Arachidonic Acid / Q000737:chemistry*; D040501:Calgranulin A / Q000737:chemistry*; D002474:Cell-Free System; D004789:Enzyme Activation; D007700:Kinetics; D019255:NADPH Oxidases / Q000737:chemistry*; D009504:Neutrophils / Q000737:chemistry*; D010586:Phagocytes / Q000201:enzymology*; D010587:Phagocytosis; D011485:Protein Binding
D040501:Calgranulin A; D016718:Arachidonic Acid; D019255:NADPH Oxidases