Alterations in cellular proteome and secretome upon differentiation from monocyte to macrophage by treatment with phorbol myristate acetate: Insights into biological processes

Sintiprungrat, Kitisak; Singhto, Nilubon; Sinchaikul, Supachok; Chen, Shui‐Tein; Thongboonkerd, Visith

doi:10.1016/j.jprot.2009.08.001

Cited by 54 publications

(45 citation statements)

References 37 publications

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“…Following stimulation of mast cells by ATP, we detected the presence of citrullinated proteins in the supernatants collected from WT but not from PAD2−/− BMMC (Figure 8). Tubulin has been described as a resident of exosomes produced by B cells and by human mesotheliomal cells and has been shown to be secreted by PMA-stimulated macrophages (44–46). Immunoblotting for tubulin provided a loading control to compare WT and PAD2 KO cell lysate and supernatant samples.…”

Section: Resultsmentioning

confidence: 99%

ATP Induces Protein Arginine Deiminase 2-Dependent Citrullination in Mast Cells through the P2X7 Purinergic Receptor

Arandjelovic

McKenney

Leming

et al. 2012

The Journal of Immunology

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Posttranslational modifications regulate physiology either by directly modulating protein function or by impacting immune recognition of self proteins. Citrullination is a posttranslational modification formed by the conversion of arginine residues into the citrulline amino acid by protein arginine deiminase (PAD) family members. We have identified mast cells as a major source of the PAD2 enzyme. Activation of the P2X7 receptor by the inflammatory “danger” signal ATP induces PAD2 activity and robust protein citrullination. P2X7-mediated activation of PAD2 is sensitive to p38 MAPK and PKC inhibitors, and PAD2 regulates the expression of the TNFR2, Adamts-9, and Rab6b transcripts in mast cells. Further, the PAD2 enzyme and its citrullinated substrate proteins are released from mast cells upon activation with ATP. PAD2 expression is closely linked with inflammation in rheumatoid arthritis (RA) synovial tissue, and PAD2 and citrullinated proteins are found in the synovial fluid of RA patients. In addition, RA is associated with the development of autoantibodies to citrullinated self proteins. Our results suggest that P2X7 activation of mast cells may play a role in inflammation by providing PAD2 and PAD2 substrates access to the extracellular space.

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Section: Resultsmentioning

confidence: 99%

ATP Induces Protein Arginine Deiminase 2-Dependent Citrullination in Mast Cells through the P2X7 Purinergic Receptor

Arandjelovic

McKenney

Leming

et al. 2012

The Journal of Immunology

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“…Also a-tubulin exists both as a cytoplasmic and as a secreted isoform. Cellular secretion of a-tubulin has been recently observed during the differentiation of monocyte to macrophage [Sintiprungrat et al, 2010] and this process has been linked to the cytoskeleton rearrangement that happens in the microtubule during monocyte/macrophage differentiation. Cytoskeleton rearrangement was observed in HUVE cells exposed to modeled microgravity a few years ago [Carlsson et al, 2003;Versari et al, 2007], but only recently [Li et al, 2009] have clearly demonstrated that low gravity rapidly disorganize microtubules in human MCF-7 cells.…”

Section: Discussionmentioning

confidence: 99%

Modification of proteins secreted by endothelial cells during modeled low gravity exposure

Griffoni

Molfetta

Fantozzi

et al. 2011

J of Cellular Biochemistry

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The exposure of the human body to microgravity, conditions that occurs during space flights, causes significant changes in the cardiovascular system. Many cell types have been involved in these changes, and the endothelium seems to play a major role. In endothelial cells (EC), it has been shown that modeled low gravity impairs nitric oxide synthesis, cell adhesion, extracellular matrix composition, cytoskeleton organization, cytokines, and growth factors secretion. Nevertheless, detailed analysis of EC physiological changes induced by microgravity exposure is still lacking. Secretome analysis is one of the most promising approaches for the identification of biomarkers directly related to the physiopathological cellular state. In this study, we analyzed in details the modifications of EC secretome by using umbilical vein endothelial (HUVE) cells exposed to modeled low gravity conditions. By adopting a two-dimensional (2-D) proteomic approach, in conjunction with a technique for the compression of the dynamic range of proteins, we observed that modeled low gravity exposure of HUVE cells affected the secretion of proteins involved in the regulation of cytoskeleton assembly. Moreover, by using Luminex® suspension array systems, we found that the low gravity condition decreased in ECs the secretion of some key pro-inflammatory cytokines, including IL-1α and IL-8, and of the pro-angiogenic factor bFGF. On the contrary, microgravity increase the secretion of two chemokines (Rantes and Eotaxin), involved in leukocytes recruitment.

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“…At present, different proteomic techniques allow for in-depth analysis of the secretome, the global pattern of secreted proteins. Secretome analysis is important in revealing complex cellular processes that require communication and signaling between the cells, and it has recently been applied to analyze the signaling pathways related to cell differentiation (19,20), cancer (21,22), and immune responses (23)(24)(25). In the present work we have characterized the secretome of human primary macrophages that have been activated simultaneously by microbial signal lipopolysaccharide (LPS) and endogenous danger signal MSU to get a global view of macrophage response to combined PAMP and DAMP stimulation.…”

Section: Monosodium Urate (Msu) Is An Endogenous Danger Signal That Imentioning

confidence: 99%

Monosodium Urate Activates Src/Pyk2/PI3 Kinase and Cathepsin Dependent Unconventional Protein Secretion From Human Primary Macrophages

Välimäki

Miettinen

Lietzén

et al. 2013

Molecular & Cellular Proteomics

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Monosodium urate (MSU) is an endogenous danger signal that is crystallized from uric acid released from injured cells. MSU is known to activate inflammatory response in macrophages but the molecular mechanisms involved have remained uncharacterized. Activated macrophages start to secrete proteins to activate immune response and to recruit other immune cells to the site of infection and/or tissue damage. Secretome characterization after activation of innate immune system is essential to unravel the details of early phases of defense responses. Here, we have analyzed the secretome of human primary macrophages stimulated with MSU using quantitative two-dimensional gel electrophoresis based proteomics as well as high-throughput qualitative GeLC-MS/MS approach combining protein separation by SDS-PAGE and protein identification by liquid chromatography-MS/MS. Both methods showed that MSU stimulation induced robust protein secretion from lipopolysaccharide-primed human macrophages. Bioinformatic analysis of the secretome data showed that MSU stimulation strongly activates unconventional, vesicle mediated protein secretion. The unconventionally secreted proteins included pro-inflammatory cytokines like IL-1␤ and IL-18, interferon-induced proteins, and danger signal proteins. Also active forms of lysosomal proteases cathepsins were secreted on MSU stimulation, and cathepsin activity was essential for MSUinduced unconventional protein secretion. Additionally, proteins associated to phosphorylation events including Src family tyrosine kinases were increased in the secretome of MSU-stimulated cells. Our functional studies demonstrated that Src, Pyk2, and PI3 kinases act upstream of cathepsins to activate the overall protein secretion from macrophages. In conclusion, we provide the first comprehensive characterization of protein secretion pathways activated by MSU in human macrophages, and reveal a novel role for cathepsins and Src, Pyk2, PI3 ki-

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Alterations in cellular proteome and secretome upon differentiation from monocyte to macrophage by treatment with phorbol myristate acetate: Insights into biological processes

Cited by 54 publications

References 37 publications

ATP Induces Protein Arginine Deiminase 2-Dependent Citrullination in Mast Cells through the P2X7 Purinergic Receptor

ATP Induces Protein Arginine Deiminase 2-Dependent Citrullination in Mast Cells through the P2X7 Purinergic Receptor

Modification of proteins secreted by endothelial cells during modeled low gravity exposure

Monosodium Urate Activates Src/Pyk2/PI3 Kinase and Cathepsin Dependent Unconventional Protein Secretion From Human Primary Macrophages

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