Dataset Information

Proteomic signature of environmental oxygen tension modulation of human macrophage polarization and functions

ABSTRACT: Macrophages are innate immune cells characterized by their plasticity and their ability to react to various environmental stimuli. These cells are involved in a multiple number of tissular functions in homeostasis and pathological contexts. According to their environment these cells could be polarized toward different states of activation which determine their functional orientation. A large part of the macrophage biology field is devoted to better define what polarizations are, from a molecular point of view. It is now accepted that a multidimensional model of polarization is needed to grasp the broad phenotype repertoire depending on various environmental signals. Oxygen tension is one of these tissular environmental parameters. We designed this study to obtain a proteomic signature of various polarizations in human monocytes derived macrophages. We also seek to explore how environmental oxygen tension varying from an atmospheric composition (18.6% O2) to a “tissular normoxia” (3% O2) could modify our classification of macrophages’ polarization. We have obtained various polarization specific proteins and oxygen sensors for human macrophages. One example is arachidonate 15-lipoxygenase (ALOX15) which is a IL4/IL13 polarization specific proteins up regulated under low oxygen exposure associated to an increase of the phagocytosis rate of apoptotic cells. These results illustrate the necessity to take into account physicochemical parameters like oxygen when macrophage polarization is studied to correctly assess their functions in tissues.

INSTRUMENT(S): impact II

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood, Macrophage

SUBMITTER: Arnaud Millet

LAB HEAD: Millet

PROVIDER: PXD006354 | Pride | 2017-09-11

REPOSITORIES: Pride

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Publications

Proteomic Signature Reveals Modulation of Human Macrophage Polarization and Functions Under Differing Environmental Oxygen Conditions.

Court Magali M Petre Graciane G Atifi Michèle El ME Millet Arnaud A

Molecular & cellular proteomics : MCP 20170908 12

Macrophages are innate immune cells which can react to a large number of environmental stimuli thanks to a high degree of plasticity. These cells are involved in a variety of tissue functions in homeostasis, and they play essential roles in pathological contexts. Macrophages' activation state, which determines their functional orientation, is strongly influenced by the cellular environment. A large body of macrophage literature is devoted to better defining polarizations from a molecular viewpoi ...[more]

PMID: 28887380

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Project description:One of the most important features of tumor microenvironment, imposing adverse effect on patient prognosis, is low oxygen tension. There are two types of hypoxia that may occur within tumor mass: chronic and cycling. Preliminary studies point at cycling hypoxia as being more relevant in induction of aggressive phenotype of tumor cells and radioresistance though little is known about the molecular mechanism of this phenomenon. Analysis of gene expression profile of human prostate (PC-3), ovarian (SK-OV-3) and melanoma (WM793B) cancer cells to expermental cycling (interchanging conditions of 1% and 21% oxygen) or chronic (1% oxygen) for 72 hours. Gene expression profiles were analyzed using U133 Plus 2.0 Array (Affymetrix) oligonucleotide microarrays. Data analysis revealed that globally gene expression profiles induced by the two types of hypoxia are similar and they strongly depend on the cell type.However, cycling hypoxia changes expression of lower number of genes in comparison to chronic one ( 3767 vs. 5954 probesets (p<0.001)) and to lower extent (lower fold changes). Analysis of hypoxia-regulated gene lists obtained using Random Variance Model t-test identified 253 probe sets (FC>2, p<0.001) common to all three cell lines, though no universal (changed throughout all analyzed cell lines) genes specifically influanced only by cycling hypoxia was selected. On the other hand, we identified such genes within particular one or two cell lines. Among them those related with EGF pathway seemed to be overrepresented (i.e. EPHA2, AREG, and HBEGF) and together with PLAU and IL-8 were mostly validated by Q-PCR. We investigated transcriptional activity of prostate and ovarian cancer cells as well as melanoma cells cultured for 72h under chronic hypoxic (nominal 1% oxygen; 3 experimental samples for each cell type), cycling hypoxia (interchanging periods of nominal 1% and 21% oxygen; 3 samples for each line) and control conditions (21% oxygen; 3 samples for each cell lines).

Dataset Information

Proteomic signature of environmental oxygen tension modulation of human macrophage polarization and functions

Publications

Proteomic Signature Reveals Modulation of Human Macrophage Polarization and Functions Under Differing Environmental Oxygen Conditions.

Similar Datasets

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