GM-CSF- and M-CSF-primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures [Research]

M1 and M2 activated macrophages (Ms) have different roles in inflammation. Because pathogens may first encounter resting cells, we investigated lipid mediator profiles prior to full activation. Human monocytes were differentiated with granulocyte M colony-stimulating factor (GM-CSF) or M colony-stimulating factor (M-CSF), which are known to prime toward M1 or M2 phenotypes, respectively. Lipid mediators released during resting conditions and produced in response to bacterial stimuli (LPS/N-formylmethionyl-leucyl-phenylalanine or peptidoglycan) were quantified by liquid chromatography-mass spectrometry. In resting conditions, both M phenotypes released primarily proresolving lipid mediators (prostaglandin E2 metabolite, lipoxin A4, and 18-hydroxyeicosapentaenoic acid). A striking shift toward proinflammatory eicosanoids was observed when the same cells were exposed (30 min) to bacterial stimuli: M-CSF Ms produced considerably more 5-lipoxygenase products, particularly leukotriene C4, potentially linked to M2 functions in asthma. Prostaglandins were formed by both M types. In the M-CSF cells, there was also an enhanced release of arachidonic acid and activation of cytosolic phospholipase A2. However, GM-CSF cells expressed higher levels of 5-lipoxygenase and 5-lipoxygenase–activating protein, and in ionophore incubations these cells also produced the highest levels of 5-hydroxyeicosatetraenoic acid. In summary, GM-CSF and M-CSF Ms displayed similar proresolving lipid medi...

Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Lukic, A., Larssen, P., Fauland, A., Samuelsson, B., Wheelock, C. E., Gabrielsson, S., Radmark, O. Tags: Research Source Type: research