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  1. Article ; Online: Administration of a Bacterial Lysate to the Airway Compartment Is Sufficient to Inhibit Allergen-Induced Lung Eosinophilia in Germ-free Mice.

    Michael, Ashley N / Pivniouk, Oksana / Ezeh, Peace C / Banskar, Sunil / Hahn, Seongmin / DeVries, Avery / O'Connell, Kathryn / Pivniouk, Vadim / Vercelli, Donata

    Journal of leukocyte biology

    2024  

    Abstract: The nexus between eosinophils and microbes is attracting increasing attention. We previously showed that airway administration of sterile microbial products contained in dust collected from traditional dairy farms virtually abrogated broncho-alveolar ... ...

    Abstract The nexus between eosinophils and microbes is attracting increasing attention. We previously showed that airway administration of sterile microbial products contained in dust collected from traditional dairy farms virtually abrogated broncho-alveolar lavage (BAL) eosinophilia and other cardinal asthma phenotypes in allergen-sensitized specific pathogen-free (SPF) mice. Interestingly, comparable inhibition of allergen-induced BAL eosinophilia and promotion of airway barrier integrity were found upon administration of a sterile, pharmacological grade bacterial lysate, OM-85, to the airway compartment of allergen-sensitized SPF mice. Here we asked whether intrinsic properties of airway-delivered microbial products were sufficient to inhibit allergic lung inflammation or whether these effects were mediated by reprogramming of the host microbiota. We compared germ-free (GF) mice and offspring of GF mice associated with healthy mouse gut microbiota and maintained under SPF conditions for multiple generations (Ex-GF mice). These mice were treated intra-nasally with OM-85 and evaluated in the OVA and Alternaria models of allergic asthma focusing primarily on BAL eosinophilia. Levels of allergen-induced BAL eosinophilia were comparable in GF and conventionalized Ex-GF mice. Airway administration of the OM-85 bacterial lysate was sufficient to inhibit allergen-induced lung eosinophilia in both Ex-GF and GF mice, suggesting that host microbiota are not required for the protective effects of bacterial products in these models and local airway exposure to microbial products is an effective source of protection. OM-85-dependent inhibition of BAL eosinophilia in GF mice was accompanied by suppression of lung type-2 cytokines and eosinophil-attracting chemokines, suggesting that OM-85 may work at least by decreasing eosinophil lung recruitment.
    Language English
    Publishing date 2024-03-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1093/jleuko/qiae047
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Evaluation of Toxicity in Mouse Bone Marrow Progenitor Cells.

    Ezeh, Peace C / Xu, Huan / Wang, Shu Chun / Medina, Sebastian / Burchiel, Scott W

    Current protocols in toxicology

    2016  Volume 67, Page(s) 18.9.1–18.9.12

    Abstract: Development of blood cells through hematopoiesis occurs in the bone marrow (BM), and can be adversely impacted by various substances and/or conditions ranging from known therapeutic, intentionally administered xenobiotics to unintentional food additives ... ...

    Abstract Development of blood cells through hematopoiesis occurs in the bone marrow (BM), and can be adversely impacted by various substances and/or conditions ranging from known therapeutic, intentionally administered xenobiotics to unintentional food additives and exposure to environmental chemicals. The principles underlying the techniques for evaluating toxicity to BM progenitors (erythroid, myeloid, and lymphoid) exploit changes in the normal hematopoietic process, biochemical cell surface and intracellular markers, as well as components of the BM microenvironment. Toxicological investigations following in vivo exposures of mice or in vitro exposures of mouse primary BM cell cultures allow the assessment of the developmental and functional integrity of BM cells, cell population shifts, and adverse biochemical effects due to toxicity. Colony forming unit (CFU) assays and flow cytometry are indispensable techniques in these toxicity studies.
    MeSH term(s) Animals ; Bone Marrow/drug effects ; Colony-Forming Units Assay ; Environmental Pollutants/toxicity ; Flow Cytometry ; Hematopoiesis/drug effects ; Mice ; Stem Cells/drug effects ; Xenobiotics/toxicity
    Chemical Substances Environmental Pollutants ; Xenobiotics
    Language English
    Publishing date 2016-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ISSN 1934-9262
    ISSN (online) 1934-9262
    DOI 10.1002/0471140856.tx1809s67
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression.

    Pivniouk, Vadim / Pivniouk, Oksana / DeVries, Avery / Uhrlaub, Jennifer L / Michael, Ashley / Pivniouk, Denis / VanLinden, Sydney R / Conway, Michelle Y / Hahn, Seongmin / Malone, Sean P / Ezeh, Peace / Churko, Jared M / Anderson, Dayna / Kraft, Monica / Nikolich-Zugich, Janko / Vercelli, Donata

    The Journal of allergy and clinical immunology

    2021  Volume 149, Issue 3, Page(s) 923–933.e6

    Abstract: Background: Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with ... ...

    Abstract Background: Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions.
    Objectives: We sought to investigate whether and how OM-85 treatment protects nonhuman primate and human epithelial cells against SARS-CoV-2.
    Methods: ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung, and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro.
    Results: OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein-pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation.
    Conclusions: OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of coronavirus disease 2019.
    MeSH term(s) Adjuvants, Immunologic/administration & dosage ; Angiotensin-Converting Enzyme 2/antagonists & inhibitors ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/immunology ; Animals ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19/virology ; Caco-2 Cells ; Cell Extracts/administration & dosage ; Cell Extracts/immunology ; Cells, Cultured ; Chlorocebus aethiops ; Down-Regulation/drug effects ; Epithelial Cells/drug effects ; Epithelial Cells/immunology ; Epithelial Cells/virology ; HEK293 Cells ; Host Microbial Interactions/drug effects ; Host Microbial Interactions/immunology ; Humans ; In Vitro Techniques ; Lung/drug effects ; Lung/immunology ; Lung/virology ; Mice ; Mice, Inbred BALB C ; Receptors, Virus/antagonists & inhibitors ; Receptors, Virus/immunology ; SARS-CoV-2/immunology ; Serine Endopeptidases/drug effects ; Serine Endopeptidases/genetics ; Serine Endopeptidases/immunology ; Transcription, Genetic/drug effects ; Transcription, Genetic/immunology ; Vero Cells
    Chemical Substances Adjuvants, Immunologic ; Broncho-Vaxom ; Cell Extracts ; Receptors, Virus ; Ace2 protein, mouse (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, mouse (EC 3.4.21.-)
    Language English
    Publishing date 2021-12-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2021.11.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis.

    Pivniouk, Vadim / Gimenes-Junior, Joao A / Ezeh, Peace / Michael, Ashley / Pivniouk, Oksana / Hahn, Seongmin / VanLinden, Sydney R / Malone, Sean P / Abidov, Amir / Anderson, Dayna / Gozdz, Justyna / DeVries, Avery / Martinez, Fernando D / Pasquali, Christian / Vercelli, Donata

    The Journal of allergy and clinical immunology

    2021  Volume 149, Issue 3, Page(s) 943–956

    Abstract: Background: Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is ... ...

    Abstract Background: Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is widely used empirically to prevent respiratory infections and a clinical trial is testing its ability to prevent asthma in high-risk children. We previously showed that intranasal administration of microbial products from farm environments abrogates experimental allergic asthma.
    Objectives: We sought to investigate whether direct administration of OM-85 to the airway compartment protects against experimental allergic asthma; and to identify protective cellular and molecular mechanisms activated through this natural route.
    Methods: Different strains of mice sensitized and challenged with ovalbumin or Alternaria received OM-85 intranasally, and cardinal cellular and molecular asthma phenotypes were measured. Airway transfer experiments assessed whether OM-85-treated dendritic cells protect allergen-sensitized, OM-85-naive mice against asthma.
    Results: Airway OM-85 administration suppressed allergic asthma in all models acting on multiple innate and adaptive immune targets: the airway epithelium/IL-33/ILC2 axis, lung allergen-induced type 2 responses, and dendritic cells whose Myd88/Trif-dependent tolerogenic reprogramming was sufficient to transfer OM-85-induced asthma protection.
    Conclusions: We provide the first demonstration that administering a standardized bacterial lysate to the airway compartment protects from experimental allergic asthma by engaging multiple immune pathways. Because protection required a cumulative dose 27- to 46-fold lower than the one reportedly active through the oral route, the efficacy of intranasal OM-85 administration may reflect its direct access to the airway mucosal networks controlling the initiation and development of allergic asthma.
    MeSH term(s) Allergens ; Animals ; Asthma ; Cell Extracts ; Dendritic Cells ; Disease Models, Animal ; Epithelium ; Humans ; Immunity, Innate ; Interleukin-33 ; Lung ; Lymphocytes ; Mice ; Mice, Inbred BALB C ; Ovalbumin
    Chemical Substances Allergens ; Broncho-Vaxom ; Cell Extracts ; Interleukin-33 ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2021-09-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2021.09.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Arsenite Interacts with Dibenzo[def,p]chrysene (DBC) at Low Levels to Suppress Bone Marrow Lymphoid Progenitors in Mice.

    Ezeh, Peace C / Lauer, Fredine T / Liu, Ke Jian / Hudson, Laurie G / Burchiel, Scott W

    Biological trace element research

    2015  Volume 166, Issue 1, Page(s) 82–88

    Abstract: Arsenite (As(+3)) and dibenzo[def,p]chrysene (DBC), a polycyclic aromatic hyrdrocarbon (PAH), are found in nature as environmental contaminants. Both are known to individually suppress the immune system of humans and mice. In order to determine their ... ...

    Abstract Arsenite (As(+3)) and dibenzo[def,p]chrysene (DBC), a polycyclic aromatic hyrdrocarbon (PAH), are found in nature as environmental contaminants. Both are known to individually suppress the immune system of humans and mice. In order to determine their potential interactive and combined immunosuppressive effects, we examined murine bone marrow (BM) immune progenitor cells' responses following combined oral exposures at very low levels of exposure to As(+3) and DBC. Oral 5-day exposure to DBC at 1 mg/kg (cumulative dose) was found to suppress mouse BM lymphoid progenitor cells, but not the myeloid progenitors. Previously established no-effect doses of As(+3) in drinking water (19 and 75 ppb for 30 days) produced more lymphoid suppression in the bone marrow when mice were concomitantly fed a low dose of DBC during the last 5 days. The lower dose (19 ppb) As(+3) had a stronger suppressive effect with DBC than the higher dose (75 ppb). Thus, the interactive toxicity of As(+3) and DBC in vivo could be As(+3) dose dependent. In vitro, the suppressive interaction of As(+3) and DBC was also evident at low concentrations (0.5 nM), but not at higher concentrations (5 nM) of As(+3). These studies show potentially important interactions between As(+3) and DBC on mouse BM at extremely low levels of exposure in vivo and in vitro.
    MeSH term(s) Animals ; Arsenites/toxicity ; Benzopyrenes/toxicity ; Bone Marrow/drug effects ; Bone Marrow/immunology ; Cell Survival/drug effects ; Colony-Forming Units Assay ; Dose-Response Relationship, Immunologic ; Drug Synergism ; Environmental Pollutants/toxicity ; Immune Tolerance/drug effects ; Lymphoid Progenitor Cells/drug effects ; Lymphoid Progenitor Cells/immunology ; Mice, Inbred C57BL
    Chemical Substances Arsenites ; Benzopyrenes ; Environmental Pollutants ; dibenzo(a,l)pyrene (G3X629VE4A) ; arsenite (N5509X556J)
    Keywords covid19
    Language English
    Publishing date 2015-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 445336-0
    ISSN 1559-0720 ; 0163-4984
    ISSN (online) 1559-0720
    ISSN 0163-4984
    DOI 10.1007/s12011-015-0279-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Monomethylarsonous acid (MMA⁺³) Inhibits IL-7 Signaling in Mouse Pre-B Cells

    Ezeh, Peace C. / Xu, Huan / Lauer, Fredine T. / Liu, Ke Jian / Hudson, Laurie G. / Burchiel, Scott W.

    Toxicological sciences. 2016 Feb., v. 149, no. 2

    2016  

    Abstract: Our previously published data show that As⁺³ in vivo and in vitro, at very low concentrations, inhibits lymphoid, but not myeloid stem cell development in mouse bone marrow. We also showed that the As⁺³ metabolite, monomethylarsonous acid (MMA⁺³), was ... ...

    Abstract Our previously published data show that As⁺³ in vivo and in vitro, at very low concentrations, inhibits lymphoid, but not myeloid stem cell development in mouse bone marrow. We also showed that the As⁺³ metabolite, monomethylarsonous acid (MMA⁺³), was responsible for the observed pre-B cell toxicity caused by As⁺³. Interleukin-7 (IL-7) is the primary growth factor responsible for pre-lymphoid development in mouse and human bone marrow, and Signal Transducer and Activator of Transcription 5 (STAT5) is a transcriptional factor in the IL-7 signaling pathway. We found that MMA⁺³ inhibited STAT5 phosphorylation at a concentration as low as 50 nM in mouse bone marrow pre-B cells. Inhibition of STAT5 phosphorylation by As⁺³ occurred only at a concentration of 500 nM. In the IL-7 dependent mouse pre-B 2E8 cell line, we also found selective inhibition of STAT5 phosphorylation by MMA⁺³, and this inhibition was dependent on effects on JAK3 phosphorylation. IL-7 receptor expression on 2E8 cell surface was also suppressed by 50 nM MMA⁺³ at 18 h. As further evidence for the inhibition of STAT5, we found that the induction of several genes required in B cell development, cyclin D1, E2A, EBF1, and PAX5, were selectively inhibited by MMA⁺³. Since 2E8 cells lack the enzymes responsible for the conversion of As⁺³ to MMA⁺³ in vitro, the results of these studies suggest that As⁺³ induced inhibition of pre-B cell formation in vivo is likely dependent on the formation of MMA⁺³ which in turn inhibits IL-7 signaling at several steps in mouse pre-B cells.
    Keywords B-lymphocytes ; bone marrow ; cell lines ; cyclins ; cytotoxicity ; humans ; interleukin-7 ; metabolites ; mice ; phosphorylation ; signal transduction ; stem cells ; toxicology ; transactivators
    Language English
    Dates of publication 2016-02
    Size p. 289-299.
    Publishing place Oxford University Press
    Document type Article
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kfv233
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Monomethylarsonous acid (MMA+3) Inhibits IL-7 Signaling in Mouse Pre-B Cells.

    Ezeh, Peace C / Xu, Huan / Lauer, Fredine T / Liu, Ke Jian / Hudson, Laurie G / Burchiel, Scott W

    Toxicological sciences : an official journal of the Society of Toxicology

    2016  Volume 149, Issue 2, Page(s) 289–299

    Abstract: Our previously published data show that As(+3) in vivo and in vitro, at very low concentrations, inhibits lymphoid, but not myeloid stem cell development in mouse bone marrow. We also showed that the As(+3) metabolite, monomethylarsonous acid (MMA(+3)), ... ...

    Abstract Our previously published data show that As(+3) in vivo and in vitro, at very low concentrations, inhibits lymphoid, but not myeloid stem cell development in mouse bone marrow. We also showed that the As(+3) metabolite, monomethylarsonous acid (MMA(+3)), was responsible for the observed pre-B cell toxicity caused by As(+3). Interleukin-7 (IL-7) is the primary growth factor responsible for pre-lymphoid development in mouse and human bone marrow, and Signal Transducer and Activator of Transcription 5 (STAT5) is a transcriptional factor in the IL-7 signaling pathway. We found that MMA(+3) inhibited STAT5 phosphorylation at a concentration as low as 50 nM in mouse bone marrow pre-B cells. Inhibition of STAT5 phosphorylation by As(+3) occurred only at a concentration of 500 nM. In the IL-7 dependent mouse pre-B 2E8 cell line, we also found selective inhibition of STAT5 phosphorylation by MMA(+3), and this inhibition was dependent on effects on JAK3 phosphorylation. IL-7 receptor expression on 2E8 cell surface was also suppressed by 50 nM MMA(+3) at 18 h. As further evidence for the inhibition of STAT5, we found that the induction of several genes required in B cell development, cyclin D1, E2A, EBF1, and PAX5, were selectively inhibited by MMA(+3). Since 2E8 cells lack the enzymes responsible for the conversion of As(+3) to MMA(+3) in vitro, the results of these studies suggest that As(+3) induced inhibition of pre-B cell formation in vivo is likely dependent on the formation of MMA(+3) which in turn inhibits IL-7 signaling at several steps in mouse pre-B cells.
    MeSH term(s) Animals ; Arsenic/toxicity ; Interleukin-7/antagonists & inhibitors ; Interleukin-7/physiology ; Janus Kinase 1/antagonists & inhibitors ; Male ; Mice ; Mice, Inbred C57BL ; Organometallic Compounds/toxicity ; Phosphorylation ; Precursor Cells, B-Lymphoid/drug effects ; Precursor Cells, B-Lymphoid/immunology ; Precursor Cells, B-Lymphoid/physiology ; STAT5 Transcription Factor/antagonists & inhibitors ; STAT5 Transcription Factor/metabolism ; Signal Transduction/drug effects
    Chemical Substances Interleukin-7 ; Organometallic Compounds ; STAT5 Transcription Factor ; interleukin-7, mouse ; monomethylarsonous acid ; Jak1 protein, mouse (EC 2.7.10.2) ; Janus Kinase 1 (EC 2.7.10.2) ; Arsenic (N712M78A8G)
    Language English
    Publishing date 2016-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kfv233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Soy lecithin replaces egg yolk for cryopreservation of human sperm without adversely affecting postthaw motility, morphology, sperm DNA integrity, or sperm binding to hyaluronate.

    Reed, Michael L / Ezeh, Peace C / Hamic, Amanda / Thompson, Douglas J / Caperton, Charles L

    Fertility and sterility

    2009  Volume 92, Issue 5, Page(s) 1787–1790

    Abstract: Semen specimens (one ejaculate from each of 20 consenting study participants) were subjected to routine semen analysis, an in vitro sperm binding assay (HBA), and a sperm chromatin dispersion assay (HaloSperm), both before and after cryopreservation ... ...

    Abstract Semen specimens (one ejaculate from each of 20 consenting study participants) were subjected to routine semen analysis, an in vitro sperm binding assay (HBA), and a sperm chromatin dispersion assay (HaloSperm), both before and after cryopreservation using cryoprotectant media supplemented with either egg yolk or soy lecithin. Comparing the equivalency of the two phospholipid cryopreservation supplements with regard to postthaw functional parameters demonstrated that there were no statistically significant differences between the two supplements for [1] recovery of motile sperm, [2] maintenance of sperm cell morphology, [3] maintenance of the ability of sperm to bind to hyaluronate in vitro, or [4] maintenance of sperm DNA integrity.
    MeSH term(s) Cryopreservation/methods ; Cryoprotective Agents/chemistry ; Cryoprotective Agents/pharmacology ; DNA/chemistry ; DNA/drug effects ; DNA Fragmentation/drug effects ; Egg Proteins/pharmacology ; Feasibility Studies ; Humans ; Hyaluronic Acid/metabolism ; Lecithins/pharmacology ; Male ; Semen Preservation/methods ; Soybean Proteins/chemistry ; Soybean Proteins/pharmacology ; Sperm Motility/drug effects ; Spermatozoa/cytology ; Spermatozoa/drug effects ; Spermatozoa/metabolism ; Spermatozoa/physiology
    Chemical Substances Cryoprotective Agents ; Egg Proteins ; Lecithins ; Soybean Proteins ; Hyaluronic Acid (9004-61-9) ; DNA (9007-49-2)
    Language English
    Publishing date 2009-11
    Publishing country United States
    Document type Evaluation Studies ; Journal Article
    ZDB-ID 80133-1
    ISSN 1556-5653 ; 0015-0282
    ISSN (online) 1556-5653
    ISSN 0015-0282
    DOI 10.1016/j.fertnstert.2009.05.026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo.

    Ezeh, Peace C / Lauer, Fredine T / MacKenzie, Debra / McClain, Shea / Liu, Ke Jian / Hudson, Laurie G / Gandolfi, A Jay / Burchiel, Scott W

    PloS one

    2014  Volume 9, Issue 4, Page(s) e93920

    Abstract: It is known that exposure to As(+3) via drinking water causes a disruption of the immune system and significantly compromises the immune response to infection. The purpose of these studies was to assess the effects of As(+3) on bone marrow progenitor ... ...

    Abstract It is known that exposure to As(+3) via drinking water causes a disruption of the immune system and significantly compromises the immune response to infection. The purpose of these studies was to assess the effects of As(+3) on bone marrow progenitor cell colony formation and the humoral immune response to a T-dependent antigen response (TDAR) in vivo. In a 30 day drinking water study, mice were exposed to 19, 75, or 300 ppb As(+3). There was a decrease in bone marrow cell recovery, but not spleen cell recovery at 300 ppb As(+3). In the bone marrow, As(+3) altered neither the expression of CD34+ and CD38+ cells, markers of early hematopoietic stem cells, nor CD45-/CD105+, markers of mesenchymal stem cells. Spleen cell surface marker CD45 expression on B cells (CD19+), T cells (CD3+), T helper cells (CD4+) and cytotoxic T cells (CD8+), natural killer (NK+), and macrophages (Mac 1+) were not altered by the 30 day in vivo As(+3) exposure. Functional assays of CFU-B colony formation showed significant selective suppression (p<0.05) by 300 ppb As(+3) exposure, whereas CFU-GM formation was not altered. The TDAR of the spleen cells was significantly suppressed at 75 and 300 ppb As(+3). In vitro studies of the bone marrow revealed a selective suppression of CFU-B by 50 nM As(+3) in the absence of apparent cytotoxicity. Monomethylarsonous acid (MMA(+3)) demonstrated a dose-dependent and selective suppression of CFU-B beginning at 5 nM (p<0.05). MMA(+3) suppressed CFU-GM formation at 500 nM, a concentration that proved to be nonspecifically cytotoxic. As(+5) did not suppress CFU-B and/or CFU-GM in vitro at concentrations up to 500 nM. Collectively, these results demonstrate that As(+3) and likely its metabolite (MMA(+3)) target lymphoid progenitor cells in mouse bone marrow and mature B and T cell activity in the spleen.
    MeSH term(s) Animals ; Arsenites/pharmacology ; Bone Marrow Cells/cytology ; Bone Marrow Cells/drug effects ; Bone Marrow Cells/immunology ; Cell Differentiation/drug effects ; Cell Differentiation/immunology ; Colony-Forming Units Assay ; Immunity, Humoral/drug effects ; Lymphoid Progenitor Cells/cytology ; Lymphoid Progenitor Cells/drug effects ; Lymphoid Progenitor Cells/immunology ; Mice ; Spleen/drug effects ; Spleen/immunology ; Teratogens/pharmacology
    Chemical Substances Arsenites ; Teratogens ; arsenite (N5509X556J)
    Keywords covid19
    Language English
    Publishing date 2014-04-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0093920
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Arsenite Interacts with Dibenzo[def,p]chrysene (DBC) at Low Levels to Suppress Bone Marrow Lymphoid Progenitors in Mice

    Ezeh, Peace C. / Lauer, Fredine T. / Liu, Ke Jian / Hudson, Laurie G. / Burchiel, Scott W.

    Biological trace element research

    Volume v. 166,, Issue no. 1

    Abstract: Arsenite (As⁺³) and dibenzo[def,p]chrysene (DBC), a polycyclic aromatic hyrdrocarbon (PAH), are found in nature as environmental contaminants. Both are known to individually suppress the immune system of humans and mice. In order to determine their ... ...

    Abstract Arsenite (As⁺³) and dibenzo[def,p]chrysene (DBC), a polycyclic aromatic hyrdrocarbon (PAH), are found in nature as environmental contaminants. Both are known to individually suppress the immune system of humans and mice. In order to determine their potential interactive and combined immunosuppressive effects, we examined murine bone marrow (BM) immune progenitor cells’ responses following combined oral exposures at very low levels of exposure to As⁺³ and DBC. Oral 5-day exposure to DBC at 1 mg/kg (cumulative dose) was found to suppress mouse BM lymphoid progenitor cells, but not the myeloid progenitors. Previously established no-effect doses of As⁺³ in drinking water (19 and 75 ppb for 30 days) produced more lymphoid suppression in the bone marrow when mice were concomitantly fed a low dose of DBC during the last 5 days. The lower dose (19 ppb) As⁺³ had a stronger suppressive effect with DBC than the higher dose (75 ppb). Thus, the interactive toxicity of As⁺³ and DBC in vivo could be As⁺³ dose dependent. In vitro, the suppressive interaction of As⁺³ and DBC was also evident at low concentrations (0.5 nM), but not at higher concentrations (5 nM) of As⁺³. These studies show potentially important interactions between As⁺³ and DBC on mouse BM at extremely low levels of exposure in vivo and in vitro.
    Keywords mice ; arsenites ; dose response ; toxicity ; stem cells ; pollution ; polycyclic aromatic hydrocarbons ; humans ; bone marrow
    Language English
    Document type Article
    ISSN 0163-4984
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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