The Experts below are selected from a list of 186105 Experts worldwide ranked by ideXlab platform
Stefan H E Kaufmann - One of the best experts on this subject based on the ideXlab platform.
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correction of the iron overload defect in beta 2 microglobulin knockout mice by lactoferrin abolishes their Increased Susceptibility to tuberculosis
Journal of Experimental Medicine, 2002Co-Authors: Ulrich E Schaible, Helen L Collins, Friedrich Priem, Stefan H E KaufmannAbstract:As a resident of early endosomal phagosomes, Mycobacterium tuberculosis is connected to the iron uptake system of the host macrophage. beta-2-microglobulin (beta2m) knockout (KO) mice are more susceptible to tuberculosis than wild-type mice, which is generally taken as a proof for the role of major histocompatibility complex class I (MHC-I)-restricted CD8 T cells in protection against M. tuberculosis. However, beta2m associates with a number of MHC-I-like proteins, including HFE. This protein regulates transferrin receptor mediated iron uptake and mutations in its gene cause hereditary iron overload (hemochromatosis). Accordingly, beta2m-deficient mice suffer from tissue iron overload. Here, we show that modulating the extracellular iron pool in beta2m-KO mice by lactoferrin treatment significantly reduces the burden of M. tuberculosis to numbers comparable to those observed in MHC class I-KO mice. In parallel, the generation of nitric oxide impaired in beta2m-KO mice was rescued. Conversely, iron overload in the immunocompetent host exacerbated disease. Consistent with this, iron deprivation in infected resting macrophages was detrimental for intracellular mycobacteria. Our data establish: (a) defective iron metabolism explains the Increased Susceptibility of beta2m-KO mice over MHC-I-KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis.
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correction of the iron overload defect in beta 2 microglobulin knockout mice by lactoferrin abolishes their Increased Susceptibility to tuberculosis
Journal of Experimental Medicine, 2002Co-Authors: Ulrich E Schaible, Helen L Collins, Friedrich Priem, Stefan H E KaufmannAbstract:As a resident of early endosomal phagosomes, Mycobacterium tuberculosis is connected to the iron uptake system of the host macrophage. β-2-microglobulin (β2m) knockout (KO) mice are more susceptible to tuberculosis than wild-type mice, which is generally taken as a proof for the role of major histocompatibility complex class I (MHC-I)–restricted CD8 T cells in protection against M. tuberculosis. However, β2m associates with a number of MHC-I–like proteins, including HFE. This protein regulates transferrin receptor mediated iron uptake and mutations in its gene cause hereditary iron overload (hemochromatosis). Accordingly, β2m-deficient mice suffer from tissue iron overload. Here, we show that modulating the extracellular iron pool in β2m–KO mice by lactoferrin treatment significantly reduces the burden of M. tuberculosis to numbers comparable to those observed in MHC class I–KO mice. In parallel, the generation of nitric oxide impaired in β2m–KO mice was rescued. Conversely, iron overload in the immunocompetent host exacerbated disease. Consistent with this, iron deprivation in infected resting macrophages was detrimental for intracellular mycobacteria. Our data establish: (a) defective iron metabolism explains the Increased Susceptibility of β2m-KO mice over MHC-I–KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis.
Michael T Chin - One of the best experts on this subject based on the ideXlab platform.
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in utero exposure to diesel exhaust air pollution promotes adverse intrauterine conditions resulting in weight gain altered blood pressure and Increased Susceptibility to heart failure in adult mice
PLOS ONE, 2014Co-Authors: Chad S Weldy, Yonggang Liu, Denny H Liggitt, Michael T ChinAbstract:Exposure to fine particulate air pollution (PM₂.₅) is strongly associated with cardiovascular morbidity and mortality. Exposure to PM₂.₅ during pregnancy promotes reduced birthweight, and the associated adverse intrauterine conditions may also promote adult risk of cardiovascular disease. Here, we investigated the potential for in utero exposure to diesel exhaust (DE) air pollution, a major source of urban PM₂.₅, to promote adverse intrauterine conditions and influence adult Susceptibility to disease. We exposed pregnant female C57Bl/6J mice to DE (≈300 µg/m³ PM₂.₅, 6 hrs/day, 5 days/week) from embryonic day (E) 0.5 to 17.5. At E17.5 embryos were collected for gravimetric analysis and assessed for evidence of resorption. Placental tissues underwent pathological examination to assess the extent of injury, inflammatory cell infiltration, and oxidative stress. In addition, some dams that were exposed to DE were allowed to give birth to pups and raise offspring in filtered air (FA) conditions. At 10-weeks of age, body weight and blood pressure were measured. At 12-weeks of age, cardiac function was assessed by echocardiography. Susceptibility to pressure overload-induced heart failure was then determined after transverse aortic constriction surgery. We found that in utero exposure to DE increases embryo resorption, and promotes placental hemorrhage, focal necrosis, compaction of labyrinth vascular spaces, inflammatory cell infiltration and oxidative stress. In addition, we observed that in utero DE exposure Increased body weight, but counterintuitively reduced blood pressure without any changes in baseline cardiac function in adult male mice. Importantly, we observed these mice to have Increased Susceptibility to pressure-overload induced heart failure, suggesting this in utero exposure to DE 'reprograms' the heart to a heightened Susceptibility to failure. These observations provide important data to suggest that developmental exposure to air pollution may strongly influence adult Susceptibility to cardiovascular disease.
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in utero exposure to diesel exhaust air pollution promotes adverse intrauterine conditions resulting in weight gain altered blood pressure and Increased Susceptibility to heart failure in adult mice
PLOS ONE, 2014Co-Authors: Chad S Weldy, Denny H Liggitt, Michael T ChinAbstract:Exposure to fine particulate air pollution (PM2.5) is strongly associated with cardiovascular morbidity and mortality. Exposure to PM2.5 during pregnancy promotes reduced birthweight, and the associated adverse intrauterine conditions may also promote adult risk of cardiovascular disease. Here, we investigated the potential for in utero exposure to diesel exhaust (DE) air pollution, a major source of urban PM2.5, to promote adverse intrauterine conditions and influence adult Susceptibility to disease. We exposed pregnant female C57Bl/6J mice to DE (≈300 µg/m3 PM2.5, 6 hrs/day, 5 days/week) from embryonic day (E) 0.5 to 17.5. At E17.5 embryos were collected for gravimetric analysis and assessed for evidence of resorption. Placental tissues underwent pathological examination to assess the extent of injury, inflammatory cell infiltration, and oxidative stress. In addition, some dams that were exposed to DE were allowed to give birth to pups and raise offspring in filtered air (FA) conditions. At 10-weeks of age, body weight and blood pressure were measured. At 12-weeks of age, cardiac function was assessed by echocardiography. Susceptibility to pressure overload-induced heart failure was then determined after transverse aortic constriction surgery. We found that in utero exposure to DE increases embryo resorption, and promotes placental hemorrhage, focal necrosis, compaction of labyrinth vascular spaces, inflammatory cell infiltration and oxidative stress. In addition, we observed that in utero DE exposure Increased body weight, but counterintuitively reduced blood pressure without any changes in baseline cardiac function in adult male mice. Importantly, we observed these mice to have Increased Susceptibility to pressure-overload induced heart failure, suggesting this in utero exposure to DE ‘reprograms’ the heart to a heightened Susceptibility to failure. These observations provide important data to suggest that developmental exposure to air pollution may strongly influence adult Susceptibility to cardiovascular disease.
Ulrich E Schaible - One of the best experts on this subject based on the ideXlab platform.
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correction of the iron overload defect in beta 2 microglobulin knockout mice by lactoferrin abolishes their Increased Susceptibility to tuberculosis
Journal of Experimental Medicine, 2002Co-Authors: Ulrich E Schaible, Helen L Collins, Friedrich Priem, Stefan H E KaufmannAbstract:As a resident of early endosomal phagosomes, Mycobacterium tuberculosis is connected to the iron uptake system of the host macrophage. beta-2-microglobulin (beta2m) knockout (KO) mice are more susceptible to tuberculosis than wild-type mice, which is generally taken as a proof for the role of major histocompatibility complex class I (MHC-I)-restricted CD8 T cells in protection against M. tuberculosis. However, beta2m associates with a number of MHC-I-like proteins, including HFE. This protein regulates transferrin receptor mediated iron uptake and mutations in its gene cause hereditary iron overload (hemochromatosis). Accordingly, beta2m-deficient mice suffer from tissue iron overload. Here, we show that modulating the extracellular iron pool in beta2m-KO mice by lactoferrin treatment significantly reduces the burden of M. tuberculosis to numbers comparable to those observed in MHC class I-KO mice. In parallel, the generation of nitric oxide impaired in beta2m-KO mice was rescued. Conversely, iron overload in the immunocompetent host exacerbated disease. Consistent with this, iron deprivation in infected resting macrophages was detrimental for intracellular mycobacteria. Our data establish: (a) defective iron metabolism explains the Increased Susceptibility of beta2m-KO mice over MHC-I-KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis.
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correction of the iron overload defect in beta 2 microglobulin knockout mice by lactoferrin abolishes their Increased Susceptibility to tuberculosis
Journal of Experimental Medicine, 2002Co-Authors: Ulrich E Schaible, Helen L Collins, Friedrich Priem, Stefan H E KaufmannAbstract:As a resident of early endosomal phagosomes, Mycobacterium tuberculosis is connected to the iron uptake system of the host macrophage. β-2-microglobulin (β2m) knockout (KO) mice are more susceptible to tuberculosis than wild-type mice, which is generally taken as a proof for the role of major histocompatibility complex class I (MHC-I)–restricted CD8 T cells in protection against M. tuberculosis. However, β2m associates with a number of MHC-I–like proteins, including HFE. This protein regulates transferrin receptor mediated iron uptake and mutations in its gene cause hereditary iron overload (hemochromatosis). Accordingly, β2m-deficient mice suffer from tissue iron overload. Here, we show that modulating the extracellular iron pool in β2m–KO mice by lactoferrin treatment significantly reduces the burden of M. tuberculosis to numbers comparable to those observed in MHC class I–KO mice. In parallel, the generation of nitric oxide impaired in β2m–KO mice was rescued. Conversely, iron overload in the immunocompetent host exacerbated disease. Consistent with this, iron deprivation in infected resting macrophages was detrimental for intracellular mycobacteria. Our data establish: (a) defective iron metabolism explains the Increased Susceptibility of β2m-KO mice over MHC-I–KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis.
Chad S Weldy - One of the best experts on this subject based on the ideXlab platform.
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in utero exposure to diesel exhaust air pollution promotes adverse intrauterine conditions resulting in weight gain altered blood pressure and Increased Susceptibility to heart failure in adult mice
PLOS ONE, 2014Co-Authors: Chad S Weldy, Yonggang Liu, Denny H Liggitt, Michael T ChinAbstract:Exposure to fine particulate air pollution (PM₂.₅) is strongly associated with cardiovascular morbidity and mortality. Exposure to PM₂.₅ during pregnancy promotes reduced birthweight, and the associated adverse intrauterine conditions may also promote adult risk of cardiovascular disease. Here, we investigated the potential for in utero exposure to diesel exhaust (DE) air pollution, a major source of urban PM₂.₅, to promote adverse intrauterine conditions and influence adult Susceptibility to disease. We exposed pregnant female C57Bl/6J mice to DE (≈300 µg/m³ PM₂.₅, 6 hrs/day, 5 days/week) from embryonic day (E) 0.5 to 17.5. At E17.5 embryos were collected for gravimetric analysis and assessed for evidence of resorption. Placental tissues underwent pathological examination to assess the extent of injury, inflammatory cell infiltration, and oxidative stress. In addition, some dams that were exposed to DE were allowed to give birth to pups and raise offspring in filtered air (FA) conditions. At 10-weeks of age, body weight and blood pressure were measured. At 12-weeks of age, cardiac function was assessed by echocardiography. Susceptibility to pressure overload-induced heart failure was then determined after transverse aortic constriction surgery. We found that in utero exposure to DE increases embryo resorption, and promotes placental hemorrhage, focal necrosis, compaction of labyrinth vascular spaces, inflammatory cell infiltration and oxidative stress. In addition, we observed that in utero DE exposure Increased body weight, but counterintuitively reduced blood pressure without any changes in baseline cardiac function in adult male mice. Importantly, we observed these mice to have Increased Susceptibility to pressure-overload induced heart failure, suggesting this in utero exposure to DE 'reprograms' the heart to a heightened Susceptibility to failure. These observations provide important data to suggest that developmental exposure to air pollution may strongly influence adult Susceptibility to cardiovascular disease.
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in utero exposure to diesel exhaust air pollution promotes adverse intrauterine conditions resulting in weight gain altered blood pressure and Increased Susceptibility to heart failure in adult mice
PLOS ONE, 2014Co-Authors: Chad S Weldy, Denny H Liggitt, Michael T ChinAbstract:Exposure to fine particulate air pollution (PM2.5) is strongly associated with cardiovascular morbidity and mortality. Exposure to PM2.5 during pregnancy promotes reduced birthweight, and the associated adverse intrauterine conditions may also promote adult risk of cardiovascular disease. Here, we investigated the potential for in utero exposure to diesel exhaust (DE) air pollution, a major source of urban PM2.5, to promote adverse intrauterine conditions and influence adult Susceptibility to disease. We exposed pregnant female C57Bl/6J mice to DE (≈300 µg/m3 PM2.5, 6 hrs/day, 5 days/week) from embryonic day (E) 0.5 to 17.5. At E17.5 embryos were collected for gravimetric analysis and assessed for evidence of resorption. Placental tissues underwent pathological examination to assess the extent of injury, inflammatory cell infiltration, and oxidative stress. In addition, some dams that were exposed to DE were allowed to give birth to pups and raise offspring in filtered air (FA) conditions. At 10-weeks of age, body weight and blood pressure were measured. At 12-weeks of age, cardiac function was assessed by echocardiography. Susceptibility to pressure overload-induced heart failure was then determined after transverse aortic constriction surgery. We found that in utero exposure to DE increases embryo resorption, and promotes placental hemorrhage, focal necrosis, compaction of labyrinth vascular spaces, inflammatory cell infiltration and oxidative stress. In addition, we observed that in utero DE exposure Increased body weight, but counterintuitively reduced blood pressure without any changes in baseline cardiac function in adult male mice. Importantly, we observed these mice to have Increased Susceptibility to pressure-overload induced heart failure, suggesting this in utero exposure to DE ‘reprograms’ the heart to a heightened Susceptibility to failure. These observations provide important data to suggest that developmental exposure to air pollution may strongly influence adult Susceptibility to cardiovascular disease.
Friedrich Priem - One of the best experts on this subject based on the ideXlab platform.
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correction of the iron overload defect in beta 2 microglobulin knockout mice by lactoferrin abolishes their Increased Susceptibility to tuberculosis
Journal of Experimental Medicine, 2002Co-Authors: Ulrich E Schaible, Helen L Collins, Friedrich Priem, Stefan H E KaufmannAbstract:As a resident of early endosomal phagosomes, Mycobacterium tuberculosis is connected to the iron uptake system of the host macrophage. beta-2-microglobulin (beta2m) knockout (KO) mice are more susceptible to tuberculosis than wild-type mice, which is generally taken as a proof for the role of major histocompatibility complex class I (MHC-I)-restricted CD8 T cells in protection against M. tuberculosis. However, beta2m associates with a number of MHC-I-like proteins, including HFE. This protein regulates transferrin receptor mediated iron uptake and mutations in its gene cause hereditary iron overload (hemochromatosis). Accordingly, beta2m-deficient mice suffer from tissue iron overload. Here, we show that modulating the extracellular iron pool in beta2m-KO mice by lactoferrin treatment significantly reduces the burden of M. tuberculosis to numbers comparable to those observed in MHC class I-KO mice. In parallel, the generation of nitric oxide impaired in beta2m-KO mice was rescued. Conversely, iron overload in the immunocompetent host exacerbated disease. Consistent with this, iron deprivation in infected resting macrophages was detrimental for intracellular mycobacteria. Our data establish: (a) defective iron metabolism explains the Increased Susceptibility of beta2m-KO mice over MHC-I-KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis.
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correction of the iron overload defect in beta 2 microglobulin knockout mice by lactoferrin abolishes their Increased Susceptibility to tuberculosis
Journal of Experimental Medicine, 2002Co-Authors: Ulrich E Schaible, Helen L Collins, Friedrich Priem, Stefan H E KaufmannAbstract:As a resident of early endosomal phagosomes, Mycobacterium tuberculosis is connected to the iron uptake system of the host macrophage. β-2-microglobulin (β2m) knockout (KO) mice are more susceptible to tuberculosis than wild-type mice, which is generally taken as a proof for the role of major histocompatibility complex class I (MHC-I)–restricted CD8 T cells in protection against M. tuberculosis. However, β2m associates with a number of MHC-I–like proteins, including HFE. This protein regulates transferrin receptor mediated iron uptake and mutations in its gene cause hereditary iron overload (hemochromatosis). Accordingly, β2m-deficient mice suffer from tissue iron overload. Here, we show that modulating the extracellular iron pool in β2m–KO mice by lactoferrin treatment significantly reduces the burden of M. tuberculosis to numbers comparable to those observed in MHC class I–KO mice. In parallel, the generation of nitric oxide impaired in β2m–KO mice was rescued. Conversely, iron overload in the immunocompetent host exacerbated disease. Consistent with this, iron deprivation in infected resting macrophages was detrimental for intracellular mycobacteria. Our data establish: (a) defective iron metabolism explains the Increased Susceptibility of β2m-KO mice over MHC-I–KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis.
