Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration

Esser, Julia; Gehrmann, Ulf; D’Alexandri, Fabio Luiz; Hidalgo-Estévez, Alicia M.; Wheelock, Craig E.; Scheynius, Annika; Gabrielsson, Susanne; Rådmark, Olof

doi:10.1016/j.jaci.2010.06.039

Cited by 211 publications

(192 citation statements)

References 43 publications

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“…For the purpose of this study we have simply confirmed the uptake of exosomes derived from DU145 prostate cancer cells into other PCa and benign cells and furthermore, transfer of exosomal CLU GFP derived from the LNCaP cell line to PC3 and LNCaP cells. Although more research is needed to investigate the mechanism involved in the uptake of exosomes by neighboring cells in the PCa microenvironment, our finding supports the previously hypothesized role of exosomes as cell-cell communication vesicles in tumor growth (54,55) cell migration (35,56,57), metastasis (58,59), and angiogenesis (60).…”

Section: Fig 2 Transmission Electron Microscopy (Tem)supporting

confidence: 88%

Exosomes as Biomarker Enriched Microvesicles: Characterization of Exosomal Proteins Derived from a Panel of Prostate Cell Lines with Distinct AR Phenotypes

Hosseini‐Beheshti

Pham

Adomat

et al. 2012

Molecular & Cellular Proteomics

198

144

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Section: Fig 2 Transmission Electron Microscopy (Tem)supporting

confidence: 88%

Exosomes as Biomarker Enriched Microvesicles: Characterization of Exosomal Proteins Derived from a Panel of Prostate Cell Lines with Distinct AR Phenotypes

Hosseini‐Beheshti

Pham

Adomat

et al. 2012

Molecular & Cellular Proteomics

198

144

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“…Western blot was performed as described by Esser et al (16). After transfer, nitrocellulose membranes (GE Healthcare) were analyzed with the following antibodies: in-house purified rabbit polyclonal against 5-lipoxygenase (5-LO, 1:500 dilution), 5-LO activating protein (FLAP) (1:300), LTA 4 hydrolase (1:700), LTC 4 synthase (1:300), 15-LO (1:500), and in-house purified chicken polyclonal against coactosin-like protein (CLP, 1:500).…”

Section: Sds-page and Western Blottingmentioning

confidence: 99%

GM‐CSF– and M‐CSF–primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures

et al. 2017

Self Cite

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M1 and M2 activated macrophages (Mfs) 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 Mf colony-stimulating factor (GM-CSF) or Mf 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 Mf phenotypes released primarily proresolving lipid mediators (prostaglandin E 2 metabolite, lipoxin A 4 , 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 Mfs produced considerably more 5-lipoxygenase products, particularly leukotriene C 4 , potentially linked to M2 functions in asthma. Prostaglandins were formed by both Mf types. In the M-CSF cells, there was also an enhanced release of arachidonic acid and activation of cytosolic phospholipase A 2 . 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 Mfs 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. FASEB J. 31, 4370-4381 (2017). www.fasebj.orgMacrophages (Mfs) orchestrate the inflammatory process from early onset to the resolution phase (1, 2). A major issue in Mf biology is to characterize functional phenotypes, currently described as a heterogeneous spectrum of activated states, from M1 to M2 (3, 4). Stimulating factors, such as cytokines and pathogens, can induce specific phenotypes: originally IFN-g + LPS activation resulted in a proinflammatory M1 state, whereas IL-4 activation induced the alternatively activated M2 state. Polarized cells express distinct markers, such as transcription factors, cytokines, and surface markers; these are the main tools to define Mf phenotypes. A number of transcripts have been reported to differ between M1 and M2 Mfs, including mRNAs for enzymes involved in eicosanoid metabolism (5).Eicosanoids originate from arachidonic acid (AA), released from membrane phospholipids by phospholipases, typically cytosolic phospholipase A 2 (cPLA 2 ) (6). Free AA is further metabolized via 3 enzymatic pathways: lipoxygenase (LO), cyclooxygenase (COX), and cyto...

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“…The presence of IgG1, IgG2c, or IgG3 in serum or purified fractions was confirmed by Western blot, as described previously (25), using primary goat anti-mouse IgG1, IgG2c, or IgG3 Abs (Southern Biotech) (1/500 in PBS Tween 20, 1% fat-free milk powder), followed by secondary rabbit antigoat IgG HRP conjugate (Bio-Rad, Hercules, CA) (1/2000 in PBS Tween 20, 1% fat-free milk powder).…”

Section: Western Blotmentioning

confidence: 99%

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

Bieren

Volpe

Kulagin

et al. 2015

The Journal of Immunology

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Infections with intestinal helminths severely impact on human and veterinary health, particularly through the damage that these large parasites inflict when migrating through host tissues. Host immunity often targets the motility of tissue-migrating helminth larvae, which ideally should be mimicked by anti-helminth vaccines. However, the mechanisms of larval trapping are still poorly defined. We have recently reported an important role for Abs in the rapid trapping of tissue-migrating larvae of the murine parasite Heligmosomoides polygyrus bakeri. Trapping was mediated by macrophages (MΦ) and involved complement, activating FcRs, and Arginase-1 (Arg1) activity. However, the receptors and Ab isotypes responsible for MΦ adherence and Arg1 induction remained unclear. Using an in vitro coculture assay of H. polygyrus bakeri larvae and bone marrow–derived MΦ, we now identify CD11b as the major complement receptor mediating MΦ adherence to the larval surface. However, larval immobilization was largely independent of CD11b and instead required the activating IgG receptor FcγRI (CD64) both in vitro and during challenge H. polygyrus bakeri infection in vivo. FcγRI signaling also contributed to the upregulation of MΦ Arg1 expression in vitro and in vivo. Finally, IgG2a/c was the major IgG subtype from early immune serum bound by FcγRI on the MΦ surface, and purified IgG2c could trigger larval immobilization and Arg1 expression in MΦ in vitro. Our findings reveal a novel role for IgG2a/c-FcγRI–driven MΦ activation in the efficient trapping of tissue-migrating helminth larvae and thus provide important mechanistic insights vital for anti-helminth vaccine development.

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Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration

Cited by 211 publications

References 43 publications

Exosomes as Biomarker Enriched Microvesicles: Characterization of Exosomal Proteins Derived from a Panel of Prostate Cell Lines with Distinct AR Phenotypes

Exosomes as Biomarker Enriched Microvesicles: Characterization of Exosomal Proteins Derived from a Panel of Prostate Cell Lines with Distinct AR Phenotypes

GM‐CSF– and M‐CSF–primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

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