Alveolar Macrophage Activation by Myeloperoxidase

Grattendick, Ken; Stuart, Rodney W.; Roberts, Erin; Lincoln, John A.; Lefkowitz, Stanley S.; Bollen, Alex; Moguilevsky, Nicole; Friedman, Herman; Lefkowitz, Doris L.

doi:10.1165/ajrcmb.26.6.4723

Cited by 63 publications

(18 citation statements)

References 31 publications

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“…MPO enhances mRNA expression of IL-1 α , IL-1 β , and TNF- α (19) and may play key roles in acute lung injury, resulting in respiratory dys-function (13). In addition, reactive oxygen intermediates produced from these cells have been shown to stimulate the production of inflammatory cytokines (19). Our study shows that NS1 and H 2 O 2 -MPO stimulate chemokine production associated with inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

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Key role of regulated upon activation normal T-cell expressed and secreted, nonstructural protein1 and myeloperoxidase in cytokine storm induced by influenza virus PR-8 (A/H1N1) infection in A549 bronchial epithelial cells

Phung

Sugamata

Uno

et al. 2011

Microbiology and Immunology

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Influenza virus infection causes severe respiratory disease such as that due to avian influenza (H5N1). Influenza A viruses proliferate in human epithelial cells, which produce inflammatory cytokines/chemokines as a “cytokine storm” attenuated with the viral nonstructural protein 1 (NS1). Cytokine/chemokine production in A549 epithelial cells infected with influenza A/H1N1 virus (PR-8) or nonstructural protein 1 (NS1) plasmid was examined in vitro. Because tumor necrosis factor-α (TNF-α) and regulated upon activation normal T-cell expressed and secreted (RANTES) are predominantly produced from cells infected with PR-8 virus, the effects of mRNA knockdown of these cytokines were investigated. Small interfering (si)TNF-α down-regulated RANTES expression and secretion of RANTES, interleukin (IL)-8, and monocyte chemotactic protein-1 (MCP-1). In addition, siRANTES suppressed interferon (IFN)-γ expression and secretion of RANTES, IL-8, and MCP-1, suggesting that TNF-α stimulates production of RANTES, IL-8, MCP-1, and IFN-γ, and RANTES also increased IL-8, MCP-1, and IFN-γ. Furthermore, administration of TNF-α promoted increased secretion of RANTES, IL-8, and MCP-1. Administration of RANTES enhanced IL-6, IL-8, and MCP-1 production without PR-8 infection. These results strongly suggest that, as an initial step, TNF-α regulates RANTES production, followed by increase of IL-6, IL-8, and MCP-1 and IFNs concentrations. At a later stage, cells transfected with viral NS1 plasmid showed production of a large amount of IL-8 and MCP-1 in the presence of the H2O2-myeloperoxidse (MPO) system, suggesting that NS1 of PR-8 may induce a “cytokine storm” from epithelial cells in the presence of an H2O2-MPO system.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, MPO activity increases in the plasma of patients with influenza virus infection (13). Neutrophil-derived MPO in the inflammation of lung infected with influenza virus causes pulmonary pathology, in which recruitment and activation of neutrophils are associated with oxidative tissue damage (19). …”

mentioning

confidence: 99%

Key role of regulated upon activation normal T-cell expressed and secreted, nonstructural protein1 and myeloperoxidase in cytokine storm induced by influenza virus PR-8 (A/H1N1) infection in A549 bronchial epithelial cells

Phung

Sugamata

Uno

et al. 2011

Microbiology and Immunology

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“…Both forms of MPO increased macrophage respiratory burst, intracellular killing of Candida albicans and TFN-α production [75]. MPO also induced the production of IL-1α and IL-1β message in the alveolar macrophages [75]. These data demonstrate that MPO could directly induce the production of proinflammatory cytokines by alveolar macrophages in the lung.…”

Section: Influence Of Mpo On Cytokine Production During Lung Inflamentioning

confidence: 96%

“…It is not clear why MPO-deficiency differentially alters responsiveness to TLR ligands in lung injury, but it could be due to either direct or indirect stimulation of different cells types that produce the cytokines. This was addressed using alveolar macrophages from rats stimulated with either active or enzymatically inactive MPO [75]. Both forms of MPO increased macrophage respiratory burst, intracellular killing of Candida albicans and TFN-α production [75].…”

Section: Influence Of Mpo On Cytokine Production During Lung Inflamentioning

confidence: 99%

“…This was addressed using alveolar macrophages from rats stimulated with either active or enzymatically inactive MPO [75]. Both forms of MPO increased macrophage respiratory burst, intracellular killing of Candida albicans and TFN-α production [75]. MPO also induced the production of IL-1α and IL-1β message in the alveolar macrophages [75].…”

Section: Influence Of Mpo On Cytokine Production During Lung Inflamentioning

confidence: 99%

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Myeloperoxidase: A new player in autoimmunity

Strzępa

Pritchard

Dittel

2017

Cellular Immunology

181

103

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Myeloperoxidase (MPO) is the most toxic enzyme found in the azurophilic granules of neutrophils. MPO utilizes H2O2 to generate hypochlorous acid (HClO) and other reactive moieties, which kill pathogens during infections. In contrast, in the setting of sterile inflammation, MPO and MPO-derived oxidants are thought to be pathogenic, promoting inflammation and causing tissue damage. In contrast, evidence also exists that MPO can limit the extent of immune responses. Elevated MPO levels and activity are observed in a number of autoimmune diseases including in the central nervous system (CNS) of multiple sclerosis (MS) and the joints of rheumatoid arthritis (RA) patients. A pathogenic role for MPO in driving autoimmune inflammation was demonstrated using mouse models. Mechanisms whereby MPO is thought to contribute to disease pathogenesis include tuning of adaptive immune responses and/or the induction of vascular permeability.

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Endogenous Myeloperoxidase Is a Mediator of Joint Inflammation and Damage in Experimental Arthritis

Odobasic

Yang

Muljadi

et al. 2014

Arthritis & Rheumatology

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Objective. Myeloperoxidase (MPO) is implicated as a local mediator of tissue damage when released extracellularly in many chronic inflammatory diseases. The purpose of this study was to explore the role of endogenous MPO in experimental rheumatoid arthritis (RA).Methods. K/BxN serum-transfer arthritis was induced in C57BL/6 wild-type (WT) and MPO knockout (MPO ؊/؊ ) mice, and disease development was assessed. MPO activity was measured in joint tissues from mice with or without K/BxN arthritis. Collagen-induced arthritis (CIA) was induced in WT and MPO ؊/؊ mice, and disease development and immune responses were examined. MPO expression was assessed in synovial biopsy samples from patients with active RA, and the effect of MPO on synovial fibroblasts was tested in vitro.Results. MPO was up-regulated in the joints of mice with K/BxN arthritis, and MPO deficiency attenuated the severity of the disease without affecting circulating cytokine levels. In CIA, MPO ؊/؊ mice had enhanced CD4؉ T cell responses and reduced frequency of regulatory T cells in the lymph nodes and spleen, as well as augmented interleukin-17A and diminished interferon-␥ secretion by collagen-stimulated splenocytes, without an effect on circulating anticollagen antibody levels. Despite enhanced adaptive immunity in secondary lymphoid organs, CIA development was attenuated in MPO ؊/؊ mice. Intracellular and extracellular MPO was detected in the synovium of patients with active RA, and human MPO enhanced the proliferation and decreased the apoptosis of synovial fibroblasts in vitro.Conclusion. MPO contributes to the development of arthritis despite suppressing adaptive immunity in secondary lymphoid organs. This suggests distinct effects of local MPO on arthritogenic effector responses.

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Alveolar Macrophage Activation by Myeloperoxidase

Cited by 63 publications

References 31 publications

Key role of regulated upon activation normal T-cell expressed and secreted, nonstructural protein1 and myeloperoxidase in cytokine storm induced by influenza virus PR-8 (A/H1N1) infection in A549 bronchial epithelial cells

Key role of regulated upon activation normal T-cell expressed and secreted, nonstructural protein1 and myeloperoxidase in cytokine storm induced by influenza virus PR-8 (A/H1N1) infection in A549 bronchial epithelial cells

Myeloperoxidase: A new player in autoimmunity

Endogenous Myeloperoxidase Is a Mediator of Joint Inflammation and Damage in Experimental Arthritis

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