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nd spreading and other functional activities of LPS-stimulated macrophages One possible answer is that there is a direct link to local ATP-production, even though global ATP levels were not affected under the conditions applied. Commonly, when glycolytic ATP-production is disturbed, cells adapt to the SB-590885 web PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19651303 use of other substrates such as fatty acids and amino acids (especially glutamine) for ATP production. It has been shown that thioglycollate elicited mouse peritoneal macrophages (which are partially M2-polarized) utilize fatty acids to fuel phagocytosis, especially when glucose is limiting. However, in LPS-stimulated PLOS ONE | www.plosone.org 12 macrophages, the mitochondrial route for ATP-production from fatty acid oxidation is overtly downregulated [8]. This suggests that LPS-stimulated macrophages do not have many alternative sources for fast supply of ATP. Moreover, the intracellular distribution of ATP may play a role. We and others have shown that adenylate kinase or creatine kinase catalyzed phosphotransfer reactions may help in the local ATP supply that is needed for remodeling of the cortical areas of cells during phagocytosis and migration [27,28,66,67]. Since it is generally accepted that actinrich membrane structures such as filopodia, lamellipodia, ruffles, and maybe also the phagocytic cup, are too thin to contain mitochondria, glucose and its breakdown via glycolysis may be the only source for local ATP production in these structures in LPSstimulated macrophages. In other cell types, glycolytic enzymes such as aldolase and GAPDH have been shown to be compartmentalized in cortical actin structures, such as pseudopodia, invadopodia, and lamellipodia, and to associate with the actin cytoskeleton [37,39,40,68,6

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Author: bet-bromodomain.