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  1. Article ; Online: Distinctive Effects of GM-CSF and M-CSF on Proliferation and Polarization of Two Major Pulmonary Macrophage Populations.

    Draijer, Christina / Penke, Loka Raghu Kumar / Peters-Golden, Marc

    Journal of immunology (Baltimore, Md. : 1950)

    2019  Volume 202, Issue 9, Page(s) 2700–2709

    Abstract: ... of AM functions throughout life, whereas M-CSF is broadly important for macrophage differentiation and ... self-renewal. However, the comparative actions of GM-CSF and M-CSF on AMs are incompletely understood ... their modulation by GM-CSF and M-CSF in murine primary AMs and IMs. CSFs increased the proliferation capacity and ...

    Abstract GM-CSF is required for alveolar macrophage (AM) development shortly after birth and for maintenance of AM functions throughout life, whereas M-CSF is broadly important for macrophage differentiation and self-renewal. However, the comparative actions of GM-CSF and M-CSF on AMs are incompletely understood. Interstitial macrophages (IMs) constitute a second major pulmonary macrophage population. However, unlike AMs, IM responses to CSFs are largely unknown. Proliferation, phenotypic identity, and M1/M2 polarization are important attributes of all macrophage populations, and in this study, we compared their modulation by GM-CSF and M-CSF in murine primary AMs and IMs. CSFs increased the proliferation capacity and upregulated antiapoptotic gene expression in AMs but not IMs. GM-CSF, but not M-CSF, reinforced the cellular identity, as identified by surface markers, of both cell types. GM-CSF, but not M-CSF, increased the expression of both M1 and M2 markers exclusively in AMs. Finally, CSFs enhanced the IFN-γ- and IL-4-induced polarization ability of AMs but not IMs. These first (to our knowledge) data comparing effects on the two pulmonary macrophage populations demonstrate that the activating actions of GM-CSF and M-CSF on primary AMs are not conserved in primary IMs.
    MeSH term(s) Animals ; Antigens, Differentiation/immunology ; Cell Proliferation/drug effects ; Granulocyte-Macrophage Colony-Stimulating Factor/immunology ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Interferon-gamma/immunology ; Interleukin-4/immunology ; Macrophage Colony-Stimulating Factor/immunology ; Macrophage Colony-Stimulating Factor/pharmacology ; Macrophages, Alveolar/cytology ; Macrophages, Alveolar/immunology ; Male ; Mice
    Chemical Substances Antigens, Differentiation ; IFNG protein, mouse ; Il4 protein, mouse ; Interleukin-4 (207137-56-2) ; Macrophage Colony-Stimulating Factor (81627-83-0) ; Interferon-gamma (82115-62-6) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
    Language English
    Publishing date 2019-03-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1801387
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Leukotrienes in Innate Immunity: Still Underappreciated after All These Years?

    Serezani, C Henrique / Divangahi, Maziar / Peters-Golden, Marc

    Journal of immunology (Baltimore, Md. : 1950)

    2023  Volume 210, Issue 3, Page(s) 221–227

    Abstract: Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase pathway of arachidonate metabolism. Though best known for their role in asthma, they have broad actions that touch on virtually every aspect of mammalian biology. In a Brief Review ... ...

    Abstract Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase pathway of arachidonate metabolism. Though best known for their role in asthma, they have broad actions that touch on virtually every aspect of mammalian biology. In a Brief Review published in the journal in 2005, we presented the existing evidence supporting a role for LTs in host defense. In this updated Brief Review, we focus on selected advances since then. We detail new insights into mechanisms and regulation of LT biosynthesis; the protective roles of LTs in the host response to diverse classes of pathogens, with an emphasis on viruses, including SARS-CoV-2; the phagocyte signal transduction mechanisms by which LTs exert their antimicrobial actions; the capacity for overexuberant LT production to promote tissue damage; and roles of LTs in the noninfectious immune-relevant conditions neuroinflammation and cancer.
    MeSH term(s) Animals ; Humans ; Arachidonate 5-Lipoxygenase/metabolism ; COVID-19 ; Eicosanoids ; Immunity, Innate ; Leukotrienes ; Mammals/metabolism ; SARS-CoV-2/metabolism
    Chemical Substances Arachidonate 5-Lipoxygenase (EC 1.13.11.34) ; Eicosanoids ; Leukotrienes
    Language English
    Publishing date 2023-01-17
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2200599
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Illuminating the lung regenerative potential of prostanoids.

    Fortier, Sean M / Penke, Loka R / Peters-Golden, Marc

    Science advances

    2022  Volume 8, Issue 12, Page(s) eabp8322

    Abstract: ... ...

    Abstract PGE
    Language English
    Publishing date 2022-03-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abp8322
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: From Biomarker to Mechanism? F2-isoprostanes in Pulmonary Fibrosis.

    Thatcher, Thomas H / Peters-Golden, Marc

    American journal of respiratory and critical care medicine

    2022  Volume 206, Issue 5, Page(s) 530–532

    MeSH term(s) Biomarkers/metabolism ; F2-Isoprostanes ; Fibroblasts/metabolism ; Humans ; Oxidative Stress ; Prostaglandins ; Pulmonary Fibrosis ; Receptors, Prostaglandin ; Receptors, Thromboxane ; Thromboxanes
    Chemical Substances Biomarkers ; F2-Isoprostanes ; Prostaglandins ; Receptors, Prostaglandin ; Receptors, Thromboxane ; Thromboxanes
    Language English
    Publishing date 2022-06-28
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202205-0914ED
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The Chemical Elucidation of Slow-Reacting Substance: Bronchospasm and Beyond.

    Peters-Golden, Marc

    Journal of immunology (Baltimore, Md. : 1950)

    2018  Volume 200, Issue 5, Page(s) 1535–1537

    MeSH term(s) Animals ; Antibodies/immunology ; Antigens/immunology ; Asthma/immunology ; Autacoids/immunology ; Bronchial Spasm/immunology ; Humans ; Muscle Contraction/immunology ; Muscle, Smooth/immunology
    Chemical Substances Antibodies ; Antigens ; Autacoids
    Language English
    Publishing date 2018-02-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1800037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: A new treatment for severe pulmonary arterial hypertension based on an old idea: inhibition of 5-lipoxygenase.

    Voelkel, Norbert F / Peters-Golden, Marc

    Pulmonary circulation

    2020  Volume 10, Issue 1, Page(s) 2045894019882635

    Abstract: It has been generally accepted that severe forms of pulmonary arterial hypertension are associated with inflammation. Plasma levels in patients with severe pulmonary arterial hypertension show elevated levels of interleukins and mediators of inflammation ...

    Abstract It has been generally accepted that severe forms of pulmonary arterial hypertension are associated with inflammation. Plasma levels in patients with severe pulmonary arterial hypertension show elevated levels of interleukins and mediators of inflammation and histologically the diseased small pulmonary arterioles show infiltrates of inflammatory and immune cells. Here, we review the literature that connects pulmonary hypertension with the arachidonic acid/5-lipoxygenase-derived leukotriens. This mostly preclinical background data together with the availability of 5-lipoxygenase inhibitors and leukotriene receptor blockers provide the rationale for testing the hypothesis that 5-lipoxygenase products contribute to the pathobiology of severe pulmonary arterial hypertension in a subgroup of patients.
    Language English
    Publishing date 2020-03-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2638089-4
    ISSN 2045-8940 ; 2045-8932
    ISSN (online) 2045-8940
    ISSN 2045-8932
    DOI 10.1177/2045894019882635
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Oxidative Inactivation of the Proteasome Augments Alveolar Macrophage Secretion of Vesicular SOCS3.

    Haggadone, Mikel D / Mancuso, Peter / Peters-Golden, Marc

    Cells

    2020  Volume 9, Issue 7

    Abstract: Extracellular vesicles (EVs) contain a diverse array of molecular cargoes that alter cellular phenotype and function following internalization by recipient cells. In the lung, alveolar macrophages (AMs) secrete EVs containing suppressor of cytokine ... ...

    Abstract Extracellular vesicles (EVs) contain a diverse array of molecular cargoes that alter cellular phenotype and function following internalization by recipient cells. In the lung, alveolar macrophages (AMs) secrete EVs containing suppressor of cytokine signaling 3 (SOCS3), a cytosolic protein that promotes homeostasis via vesicular transfer to neighboring alveolar epithelial cells. Although changes in the secretion of EV molecules-including but not limited to SOCS3-have been described in response to microenvironmental stimuli, the cellular and molecular machinery that control alterations in vesicular cargo packaging remain poorly understood. Furthermore, the use of quantitative methods to assess the sorting of cytosolic cargo molecules into EVs is lacking. Here, we utilized cigarette smoke extract (CSE) exposure of AMs as an in vitro model of oxidative stress to address these gaps in knowledge. We demonstrate that the accumulation of reactive oxygen species (ROS) in AMs was sufficient to augment vesicular SOCS3 release in this model. Using nanoparticle tracking analysis (NTA) in tandem with a new carboxyfluorescein succinimidyl ester (CFSE)-based intracellular protein packaging assay, we show that the stimulatory effects of CSE were at least in part attributable to elevated amounts of SOCS3 packaged per EV secreted by AMs. Furthermore, the use of a 20S proteasome activity assay alongside treatment of AMs with conventional proteasome inhibitors strongly suggest that ROS stimulated SOCS3 release via inactivation of the proteasome. These data demonstrate that tuning of AM proteasome function by microenvironmental oxidants is a critical determinant of the packaging and secretion of cytosolic SOCS3 protein within EVs.
    MeSH term(s) Animals ; Cells, Cultured ; Extracellular Vesicles/metabolism ; Female ; Macrophages, Alveolar/drug effects ; Macrophages, Alveolar/metabolism ; Oxidants/toxicity ; Oxidative Stress ; Proteasome Endopeptidase Complex/metabolism ; Rats ; Rats, Wistar ; Reactive Oxygen Species/metabolism ; Secretory Pathway ; Suppressor of Cytokine Signaling 3 Protein/metabolism ; Tobacco Smoke Pollution/adverse effects
    Chemical Substances Oxidants ; Reactive Oxygen Species ; Socs3 protein, rat ; Suppressor of Cytokine Signaling 3 Protein ; Tobacco Smoke Pollution ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2020-06-30
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9071589
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: MAP kinase phosphatase-1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution.

    Fortier, Sean M / Walker, Natalie M / Penke, Loka R / Baas, Jared D / Shen, Qinxue / Speth, Jennifer M / Huang, Steven K / Zemans, Rachel L / Bennett, Anton M / Peters-Golden, Marc

    The Journal of clinical investigation

    2024  

    Abstract: Fibrosis following tissue injury is distinguished from normal repair by the accumulation of pathogenic and apoptosis-resistant myofibroblasts (MFs), which arise primarily by differentiation from resident fibroblasts. Endogenous molecular brakes that ... ...

    Abstract Fibrosis following tissue injury is distinguished from normal repair by the accumulation of pathogenic and apoptosis-resistant myofibroblasts (MFs), which arise primarily by differentiation from resident fibroblasts. Endogenous molecular brakes that promote MF dedifferentiation and clearance during spontaneous resolution of experimental lung fibrosis may provide insights that could inform and improve treatment of progressive pulmonary fibrosis in patients. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) influences cellular phenotype and fate through precise and timely regulation of MAPK activity within various cell types and tissues, yet its role in lung fibroblasts and pulmonary fibrosis has not been explored. Utilizing gain- and loss-of-function studies, we found that MKP1 promoted lung MF dedifferentiation and restored their sensitivity to apoptosis - effects determined to be mainly dependent upon its dephosphorylation of p38α MAPK (p38α). Fibroblast-specific deletion of MKP1 following peak bleomycin-induced lung fibrosis largely abrogated its subsequent spontaneous resolution. Such resolution was restored by treating these transgenic mice with the p38α inhibitor VX-702. We conclude that MKP1 is a critical antifibrotic brake whose inhibition of pathogenic p38α in lung fibroblasts is necessary for fibrosis resolution following lung injury.
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI172826
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Alveolar Macrophages in Allergic Asthma: the Forgotten Cell Awakes.

    Draijer, Christina / Peters-Golden, Marc

    Current allergy and asthma reports

    2017  Volume 17, Issue 2, Page(s) 12

    Abstract: Purpose of review: The role of alveolar macrophages in innate immune responses has long been appreciated. Here, we review recent studies evaluating the participation of these cells in allergic inflammation.: Recent findings: Immediately after ... ...

    Abstract Purpose of review: The role of alveolar macrophages in innate immune responses has long been appreciated. Here, we review recent studies evaluating the participation of these cells in allergic inflammation.
    Recent findings: Immediately after allergen exposure, monocytes are rapidly recruited from the bloodstream and serve to promote acute inflammation. By contrast, resident alveolar macrophages play a predominantly suppressive role in an effort to restore homeostasis. As inflammation becomes established after repeated exposures, alveolar macrophages can polarize across a continuum of activation phenotypes, losing their suppressive functions and gaining pathogenic functions. Future research should focus on the diverse roles of monocytes/macrophages during various types and phases of allergic inflammation. These properties could lead us to new therapeutic opportunities.
    MeSH term(s) Animals ; Asthma/immunology ; Asthma/pathology ; Humans ; Inflammation/immunology ; Inflammation/pathology ; Macrophages, Alveolar/immunology
    Language English
    Publishing date 2017-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057370-4
    ISSN 1534-6315 ; 1529-7322
    ISSN (online) 1534-6315
    ISSN 1529-7322
    DOI 10.1007/s11882-017-0681-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Molecular determinants of mesenchymal cell activation in fibroproliferative diseases.

    Penke, Loka R / Peters-Golden, Marc

    Cellular and molecular life sciences : CMLS

    2019  Volume 76, Issue 21, Page(s) 4179–4201

    Abstract: Uncontrolled scarring, or fibrosis, can interfere with the normal function of virtually all tissues of the body, ultimately leading to organ failure and death. Fibrotic diseases represent a major cause of death in industrialized countries. Unfortunately, ...

    Abstract Uncontrolled scarring, or fibrosis, can interfere with the normal function of virtually all tissues of the body, ultimately leading to organ failure and death. Fibrotic diseases represent a major cause of death in industrialized countries. Unfortunately, no curative treatments for these conditions are yet available, highlighting the critical need for a better fundamental understanding of molecular mechanisms that may be therapeutically tractable. The ultimate indispensable effector cells responsible for deposition of extracellular matrix proteins that comprise scars are mesenchymal cells, namely fibroblasts and myofibroblasts. In this review, we focus on the biology of these cells and the molecular mechanisms that regulate their pertinent functions. We discuss key pro-fibrotic mediators, signaling pathways, and transcription factors that dictate their activation and persistence. Because of their possible clinical and therapeutic relevance, we also consider potential brakes on mesenchymal cell activation and cellular processes that may facilitate myofibroblast clearance from fibrotic tissue-topics that have in general been understudied.
    MeSH term(s) Cell Differentiation ; Extracellular Matrix/metabolism ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Fibrosis ; Humans ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Myofibroblasts/cytology ; Myofibroblasts/metabolism ; RNA, Untranslated/metabolism ; Signal Transduction
    Chemical Substances RNA, Untranslated
    Language English
    Publishing date 2019-09-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-019-03212-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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