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GM-CSF- and M-CSF-primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2017 Oct; Vol. 31 (10), pp. 4370-4381. Date of Electronic Publication: 2017 Jun 21. - Publication Year :
- 2017
-
Abstract
- M1 and M2 activated macrophages (Mϕs) 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 Mϕ colony-stimulating factor (GM-CSF) or Mϕ 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 Mϕ phenotypes released primarily proresolving lipid mediators (prostaglandin E <subscript>2</subscript> metabolite, lipoxin A <subscript>4</subscript> , 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 Mϕs produced considerably more 5-lipoxygenase products, particularly leukotriene C <subscript>4</subscript> , potentially linked to M2 functions in asthma. Prostaglandins were formed by both Mϕ types. In the M-CSF cells, there was also an enhanced release of arachidonic acid and activation of cytosolic phospholipase A <subscript>2</subscript> 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 Mϕs displayed similar proresolving lipid mediator formation in resting conditions but shifted toward different proinflammatory eicosanoids upon bacterial stimuli. This demonstrates that preference for specific eicosanoid pathways is primed by CSFs before full M1/M2 activation.-Lukic, A., Larssen, P., Fauland, A., Samuelsson, B., Wheelock, C. E., Gabrielsson, S., Radmark, O. GM-CSF- and M-CSF-primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures.<br /> (© FASEB.)
- Subjects :
- Arachidonate 5-Lipoxygenase metabolism
Eicosanoids metabolism
Granulocyte-Macrophage Colony-Stimulating Factor metabolism
Humans
Inflammation metabolism
Macrophage Colony-Stimulating Factor metabolism
Macrophages metabolism
Monocytes metabolism
Neutrophils drug effects
Neutrophils metabolism
Platelet Activating Factor metabolism
Cell Differentiation drug effects
Granulocyte-Macrophage Colony-Stimulating Factor pharmacology
Lipid Metabolism drug effects
Macrophage Colony-Stimulating Factor pharmacology
Macrophages drug effects
Monocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 31
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 28637652
- Full Text :
- https://doi.org/10.1096/fj.201700319R