The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform
Chang-kiu Moon - One of the best experts on this subject based on the ideXlab platform.
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Respiratory effect of acute and subacute exposure to Endotoxin-contaminated metal working fluid (MWF) aerosols on Sprague-Dawley rats
Archives of Toxicology, 2005Co-Authors: Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Male Sprague-Dawley rats were exposed to a water-soluble metal working fluid (MWF) (5% v/v) contaminated with Endotoxins (10,000 eu/ml or 100,000 eu/ml) at 10 mg/m3 for six hours per day for three days (acute exposure) or two weeks (subacute exposure). The geometric mean diameter of the MWF aerosols was 1.56 μm, and the airborne Endotoxin concentrations ranged from 1,231 to 2,173 eu/m3 (10,000 eu/ml in the bulk MWF) for the low dose and 19,263–27,386 eu/m3 (100,000 eu/ml in the bulk MWF) for the high dose. Minimal effects were observed after exposure to 10 mg/m3 of the MWF without Endotoxins for three days or two weeks. However, an increase in the number of polymorphonuclear cells (PMNs) and the level of protein was noted in the bronchoalveolar lavage (BAL) fluid from the rats acutely exposed to the MWF with Endotoxins. The acute exposure produced a greater increase in the number of PMNs and total cell number in the BAL fluid than the subacute exposure. The number of white blood cells in the peripheral blood and the weight of the lungs both increased after the subacute exposure to the MWF aerosol with Endotoxins, indicating increased vascular permeability in response to the Endotoxin exposure. The levels of cyotokines such as IL-4, INF-γ, and IL-1β in the BAL fluid from the rats exposed to the MWF with or without Endotoxins remained unchanged. Although the level of nitric oxide (NOx) in the BAL supernatant did not show any change, the induction of NOx from the alveolar macrophages increased in the rats acutely or subacutely exposed to the MWF contaminated with Endotoxins. The ConA-induced proliferation response showed no change, yet the LPS-induced proliferation response was significantly increased in the splenocytes from the rats subacutely exposed to the MWF with and without Endotoxins. The level of TNF-α in the spleen cell culture obtained from the rats exposed to the MWF with or without Endotoxins increased without changing the levels of IL-1β, IL-4, and INF-γ. The level of Endotoxin-specific IgE in the serum obtained from the rats exposed to the MWF with Endotoxins increased dose-dependently, while the levels of total immunoglobulins (IgG1, IgG2a and IgE) and Endotoxin-specific IgG1 and IgG2a remained unchanged. Accordingly, the current results indicate that lung inflammation can be immediately induced by acute or subacute exposure to an MWF contaminated with Endotoxins, and macrophages would appear to play a role in the induction of inflammation along with B-cell functions rather than T-cell functions, after subacute exposure to an MWF with Endotoxins. In addition, Endotoxin-specific IgE is an early marker for Endotoxin exposure in the workplace.
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inflammatory and immunological responses to subchronic exposure to Endotoxin contaminated metalworking fluid aerosols in f344 rats
Environmental Toxicology, 2005Co-Authors: Il Je Yu, Mingu Kang, Daniel R Marshak, Changkiu Moon, Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Rats were exposed for 6 h per day in inhalation chambers to a 10 mg/m3 concentration of metalworking fluid (MWF) contaminated with Endotoxin at concentrations of 1813 (low dose) and 20,250 eu/m3 (high dose) 5 days per week for 8 weeks. It was found that 94.7% of the MWF aerosol particles had diameters in the range of 0.42–4.6 μm, with geometric mean diameter of 1.56 μm. The body weight and pulmonary function parameters were measured every week during the 8 weeks of exposure, whereas bronchoalveolar lavage (BAL) fluid was prepared to measure the inflammatory markers and cytokines after the 8 weeks of exposure. There were no changes in body weight and respiratory function (tidal volume and respiratory frequency) during the 8 weeks of exposure to the MWF containing Endotoxins, yet lung weight increased significantly (P < 0.05) in the rats exposed to the MWF both with and without Endotoxins. The number of polymorphonuclear (PMN) cells in the BAL fluid increased significantly (P < 0.05) in the rats exposed to MWF with Endotoxins, and the levels of cytokines such as IL-4, INF-γ, IL-1β, and TNF-α also were significantly increased (P < 0.05) compared to the control. The NOx production activity of the BAL cells increased significantly (P < 0.05) in the rats exposed to the MWF with and without Endotoxins. Increases in lung weight, number of PMN cells, and levels of extracellular cytokines and NOx were all more significant in the rats exposed to the MWF with Endotoxins rather than in those exposed to MWF without Endotoxins. In spleen cell cultures, T-cell proliferation activity was decreased, yet cytokine levels (INF-γ, IL-1β, IL-4, and TNF-α) remained unchanged after repeated exposure to MWF with and without Endotoxins. Although the levels of total IgG1, IgG2a, and IgE antibodies in the serum were not changed, the levels of Endotoxin-specific antibodies, including IgG2a and IgE, were increased significantly (P < 0.05) in the rats exposed to Endotoxins, but there was not a significant increase in Endotoxin-specific IgG1. When taken together, the results indicate that lung inflammatory responses can be induced without changing pulmonary function after repeated exposure to MWFs contaminated with Endotoxins. In addition, Endotoxin-specific IgG2a and IgE may be effective biomarkers for workers exposed to MWFs contaminated with Endotoxins in the workplace. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 212–218, 2005.
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inflammatory and immunological responses to subchronic exposure to Endotoxin contaminated metalworking fluid aerosols in f344 rats
Environmental Toxicology, 2005Co-Authors: Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Rats were exposed for 6 h per day in inhalation chambers to a 10 mg/m3 concentration of metalworking fluid (MWF) contaminated with Endotoxin at concentrations of 1813 (low dose) and 20,250 eu/m3 (high dose) 5 days per week for 8 weeks. It was found that 94.7% of the MWF aerosol particles had diameters in the range of 0.42–4.6 μm, with geometric mean diameter of 1.56 μm. The body weight and pulmonary function parameters were measured every week during the 8 weeks of exposure, whereas bronchoalveolar lavage (BAL) fluid was prepared to measure the inflammatory markers and cytokines after the 8 weeks of exposure. There were no changes in body weight and respiratory function (tidal volume and respiratory frequency) during the 8 weeks of exposure to the MWF containing Endotoxins, yet lung weight increased significantly (P < 0.05) in the rats exposed to the MWF both with and without Endotoxins. The number of polymorphonuclear (PMN) cells in the BAL fluid increased significantly (P < 0.05) in the rats exposed to MWF with Endotoxins, and the levels of cytokines such as IL-4, INF-γ, IL-1β, and TNF-α also were significantly increased (P < 0.05) compared to the control. The NOx production activity of the BAL cells increased significantly (P < 0.05) in the rats exposed to the MWF with and without Endotoxins. Increases in lung weight, number of PMN cells, and levels of extracellular cytokines and NOx were all more significant in the rats exposed to the MWF with Endotoxins rather than in those exposed to MWF without Endotoxins. In spleen cell cultures, T-cell proliferation activity was decreased, yet cytokine levels (INF-γ, IL-1β, IL-4, and TNF-α) remained unchanged after repeated exposure to MWF with and without Endotoxins. Although the levels of total IgG1, IgG2a, and IgE antibodies in the serum were not changed, the levels of Endotoxin-specific antibodies, including IgG2a and IgE, were increased significantly (P < 0.05) in the rats exposed to Endotoxins, but there was not a significant increase in Endotoxin-specific IgG1. When taken together, the results indicate that lung inflammatory responses can be induced without changing pulmonary function after repeated exposure to MWFs contaminated with Endotoxins. In addition, Endotoxin-specific IgG2a and IgE may be effective biomarkers for workers exposed to MWFs contaminated with Endotoxins in the workplace. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 212–218, 2005.
Mariel Donzeau - One of the best experts on this subject based on the ideXlab platform.
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Research paper Simultaneous metal chelate affinity purification and Endotoxin clearance of recombinant antibody fragments
2020Co-Authors: Timo Zimmerman, Marion Satzger, Monika Raba, Manuela Weisbach, Katrin Döhn, Andreas Popp, Corinne Petit Frère, Mariel DonzeauAbstract:Endotoxins are frequent contaminants of recombinant proteins produced in Escherichia coli. Due to their adverse effects, Endotoxins have to be removed from recombinant proteins prior their use in cell-based assays or parenteral application. Reduction of Endotoxin to less than 10 EU mg �1 is, however, one of the most problematic steps during protein purification from E. coli and often associated with substantial loss of biological materials. The present paper describes the use of a single step procedure enabling metal chelate affinity purification and Endotoxin clearance from antibody fragments produced in E. coli using a non-ionic detergent. Endotoxin content was as low as 5 to 9 EU mg �1 with a recovery of antibody fragments of over 90%. Non-ionic detergent treatment did not compromise integrity and functionality of these multimeric molecules. Furthermore, recombinant antibody fragments did not stimulate Endotoxin-sensitive cell lines confirming the low Endotoxin content. In conclusion, this onestep protocol is a rapid, cost effective and automation-compatible procedure suitable for recombinant antibody fragments.
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Simultaneous metal chelate affinity purification and Endotoxin clearance of recombinant antibody fragments.
Journal of immunological methods, 2006Co-Authors: Timo Zimmerman, Marion Satzger, Monika Raba, Manuela Weisbach, Katrin Döhn, Andreas Popp, Corinne Petit-frère, Mariel DonzeauAbstract:Endotoxins are frequent contaminants of recombinant proteins produced in Escherichia coli. Due to their adverse effects, Endotoxins have to be removed from recombinant proteins prior their use in cell-based assays or parenteral application. Reduction of Endotoxin to less than 10 EU mg(-1) is, however, one of the most problematic steps during protein purification from E. coli and often associated with substantial loss of biological materials. The present paper describes the use of a single step procedure enabling metal chelate affinity purification and Endotoxin clearance from antibody fragments produced in E. coli using a non-ionic detergent. Endotoxin content was as low as 5 to 9 EU mg(-1) with a recovery of antibody fragments of over 90%. Non-ionic detergent treatment did not compromise integrity and functionality of these multimeric molecules. Furthermore, recombinant antibody fragments did not stimulate Endotoxin-sensitive cell lines confirming the low Endotoxin content. In conclusion, this one-step protocol is a rapid, cost effective and automation-compatible procedure suitable for recombinant antibody fragments.
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Single step protocol to purify recombinant proteins with low Endotoxin contents.
Protein Expression and Purification, 2006Co-Authors: Peter Reichelt, Christoph Schwarz, Mariel DonzeauAbstract:Endotoxin is an unwanted by product of recombinant proteins purified from Escherichia coli. The inherent toxicity of Endotoxins makes their removal an important step for the proteins' application in several biological assays and for safe parenteral administration. The method described in this paper is a one-step protocol which is effective at removing tightly bound Endotoxin from over-expressed tagged proteins in E. coli. We combined affinity chromatography with a non-ionic detergent washing step, to remove most of the Endotoxin contaminants from the end product. An Endotoxin reduction of less than 4 to 0.2 EU mg(-1) was achieved with protein recovery close to a yield 100%. As this new protocol requires only one step to simultaneously purify tagged proteins and eliminate Endotoxins, it represents a substantial advantage in time, effort, and expense.
Il Je Yu - One of the best experts on this subject based on the ideXlab platform.
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Respiratory effect of acute and subacute exposure to Endotoxin-contaminated metal working fluid (MWF) aerosols on Sprague-Dawley rats
Archives of Toxicology, 2005Co-Authors: Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Male Sprague-Dawley rats were exposed to a water-soluble metal working fluid (MWF) (5% v/v) contaminated with Endotoxins (10,000 eu/ml or 100,000 eu/ml) at 10 mg/m3 for six hours per day for three days (acute exposure) or two weeks (subacute exposure). The geometric mean diameter of the MWF aerosols was 1.56 μm, and the airborne Endotoxin concentrations ranged from 1,231 to 2,173 eu/m3 (10,000 eu/ml in the bulk MWF) for the low dose and 19,263–27,386 eu/m3 (100,000 eu/ml in the bulk MWF) for the high dose. Minimal effects were observed after exposure to 10 mg/m3 of the MWF without Endotoxins for three days or two weeks. However, an increase in the number of polymorphonuclear cells (PMNs) and the level of protein was noted in the bronchoalveolar lavage (BAL) fluid from the rats acutely exposed to the MWF with Endotoxins. The acute exposure produced a greater increase in the number of PMNs and total cell number in the BAL fluid than the subacute exposure. The number of white blood cells in the peripheral blood and the weight of the lungs both increased after the subacute exposure to the MWF aerosol with Endotoxins, indicating increased vascular permeability in response to the Endotoxin exposure. The levels of cyotokines such as IL-4, INF-γ, and IL-1β in the BAL fluid from the rats exposed to the MWF with or without Endotoxins remained unchanged. Although the level of nitric oxide (NOx) in the BAL supernatant did not show any change, the induction of NOx from the alveolar macrophages increased in the rats acutely or subacutely exposed to the MWF contaminated with Endotoxins. The ConA-induced proliferation response showed no change, yet the LPS-induced proliferation response was significantly increased in the splenocytes from the rats subacutely exposed to the MWF with and without Endotoxins. The level of TNF-α in the spleen cell culture obtained from the rats exposed to the MWF with or without Endotoxins increased without changing the levels of IL-1β, IL-4, and INF-γ. The level of Endotoxin-specific IgE in the serum obtained from the rats exposed to the MWF with Endotoxins increased dose-dependently, while the levels of total immunoglobulins (IgG1, IgG2a and IgE) and Endotoxin-specific IgG1 and IgG2a remained unchanged. Accordingly, the current results indicate that lung inflammation can be immediately induced by acute or subacute exposure to an MWF contaminated with Endotoxins, and macrophages would appear to play a role in the induction of inflammation along with B-cell functions rather than T-cell functions, after subacute exposure to an MWF with Endotoxins. In addition, Endotoxin-specific IgE is an early marker for Endotoxin exposure in the workplace.
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inflammatory and immunological responses to subchronic exposure to Endotoxin contaminated metalworking fluid aerosols in f344 rats
Environmental Toxicology, 2005Co-Authors: Il Je Yu, Mingu Kang, Daniel R Marshak, Changkiu Moon, Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Rats were exposed for 6 h per day in inhalation chambers to a 10 mg/m3 concentration of metalworking fluid (MWF) contaminated with Endotoxin at concentrations of 1813 (low dose) and 20,250 eu/m3 (high dose) 5 days per week for 8 weeks. It was found that 94.7% of the MWF aerosol particles had diameters in the range of 0.42–4.6 μm, with geometric mean diameter of 1.56 μm. The body weight and pulmonary function parameters were measured every week during the 8 weeks of exposure, whereas bronchoalveolar lavage (BAL) fluid was prepared to measure the inflammatory markers and cytokines after the 8 weeks of exposure. There were no changes in body weight and respiratory function (tidal volume and respiratory frequency) during the 8 weeks of exposure to the MWF containing Endotoxins, yet lung weight increased significantly (P < 0.05) in the rats exposed to the MWF both with and without Endotoxins. The number of polymorphonuclear (PMN) cells in the BAL fluid increased significantly (P < 0.05) in the rats exposed to MWF with Endotoxins, and the levels of cytokines such as IL-4, INF-γ, IL-1β, and TNF-α also were significantly increased (P < 0.05) compared to the control. The NOx production activity of the BAL cells increased significantly (P < 0.05) in the rats exposed to the MWF with and without Endotoxins. Increases in lung weight, number of PMN cells, and levels of extracellular cytokines and NOx were all more significant in the rats exposed to the MWF with Endotoxins rather than in those exposed to MWF without Endotoxins. In spleen cell cultures, T-cell proliferation activity was decreased, yet cytokine levels (INF-γ, IL-1β, IL-4, and TNF-α) remained unchanged after repeated exposure to MWF with and without Endotoxins. Although the levels of total IgG1, IgG2a, and IgE antibodies in the serum were not changed, the levels of Endotoxin-specific antibodies, including IgG2a and IgE, were increased significantly (P < 0.05) in the rats exposed to Endotoxins, but there was not a significant increase in Endotoxin-specific IgG1. When taken together, the results indicate that lung inflammatory responses can be induced without changing pulmonary function after repeated exposure to MWFs contaminated with Endotoxins. In addition, Endotoxin-specific IgG2a and IgE may be effective biomarkers for workers exposed to MWFs contaminated with Endotoxins in the workplace. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 212–218, 2005.
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inflammatory and immunological responses to subchronic exposure to Endotoxin contaminated metalworking fluid aerosols in f344 rats
Environmental Toxicology, 2005Co-Authors: Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Rats were exposed for 6 h per day in inhalation chambers to a 10 mg/m3 concentration of metalworking fluid (MWF) contaminated with Endotoxin at concentrations of 1813 (low dose) and 20,250 eu/m3 (high dose) 5 days per week for 8 weeks. It was found that 94.7% of the MWF aerosol particles had diameters in the range of 0.42–4.6 μm, with geometric mean diameter of 1.56 μm. The body weight and pulmonary function parameters were measured every week during the 8 weeks of exposure, whereas bronchoalveolar lavage (BAL) fluid was prepared to measure the inflammatory markers and cytokines after the 8 weeks of exposure. There were no changes in body weight and respiratory function (tidal volume and respiratory frequency) during the 8 weeks of exposure to the MWF containing Endotoxins, yet lung weight increased significantly (P < 0.05) in the rats exposed to the MWF both with and without Endotoxins. The number of polymorphonuclear (PMN) cells in the BAL fluid increased significantly (P < 0.05) in the rats exposed to MWF with Endotoxins, and the levels of cytokines such as IL-4, INF-γ, IL-1β, and TNF-α also were significantly increased (P < 0.05) compared to the control. The NOx production activity of the BAL cells increased significantly (P < 0.05) in the rats exposed to the MWF with and without Endotoxins. Increases in lung weight, number of PMN cells, and levels of extracellular cytokines and NOx were all more significant in the rats exposed to the MWF with Endotoxins rather than in those exposed to MWF without Endotoxins. In spleen cell cultures, T-cell proliferation activity was decreased, yet cytokine levels (INF-γ, IL-1β, IL-4, and TNF-α) remained unchanged after repeated exposure to MWF with and without Endotoxins. Although the levels of total IgG1, IgG2a, and IgE antibodies in the serum were not changed, the levels of Endotoxin-specific antibodies, including IgG2a and IgE, were increased significantly (P < 0.05) in the rats exposed to Endotoxins, but there was not a significant increase in Endotoxin-specific IgG1. When taken together, the results indicate that lung inflammatory responses can be induced without changing pulmonary function after repeated exposure to MWFs contaminated with Endotoxins. In addition, Endotoxin-specific IgG2a and IgE may be effective biomarkers for workers exposed to MWFs contaminated with Endotoxins in the workplace. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 212–218, 2005.
Daniel R. Marshak - One of the best experts on this subject based on the ideXlab platform.
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Respiratory effect of acute and subacute exposure to Endotoxin-contaminated metal working fluid (MWF) aerosols on Sprague-Dawley rats
Archives of Toxicology, 2005Co-Authors: Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Male Sprague-Dawley rats were exposed to a water-soluble metal working fluid (MWF) (5% v/v) contaminated with Endotoxins (10,000 eu/ml or 100,000 eu/ml) at 10 mg/m3 for six hours per day for three days (acute exposure) or two weeks (subacute exposure). The geometric mean diameter of the MWF aerosols was 1.56 μm, and the airborne Endotoxin concentrations ranged from 1,231 to 2,173 eu/m3 (10,000 eu/ml in the bulk MWF) for the low dose and 19,263–27,386 eu/m3 (100,000 eu/ml in the bulk MWF) for the high dose. Minimal effects were observed after exposure to 10 mg/m3 of the MWF without Endotoxins for three days or two weeks. However, an increase in the number of polymorphonuclear cells (PMNs) and the level of protein was noted in the bronchoalveolar lavage (BAL) fluid from the rats acutely exposed to the MWF with Endotoxins. The acute exposure produced a greater increase in the number of PMNs and total cell number in the BAL fluid than the subacute exposure. The number of white blood cells in the peripheral blood and the weight of the lungs both increased after the subacute exposure to the MWF aerosol with Endotoxins, indicating increased vascular permeability in response to the Endotoxin exposure. The levels of cyotokines such as IL-4, INF-γ, and IL-1β in the BAL fluid from the rats exposed to the MWF with or without Endotoxins remained unchanged. Although the level of nitric oxide (NOx) in the BAL supernatant did not show any change, the induction of NOx from the alveolar macrophages increased in the rats acutely or subacutely exposed to the MWF contaminated with Endotoxins. The ConA-induced proliferation response showed no change, yet the LPS-induced proliferation response was significantly increased in the splenocytes from the rats subacutely exposed to the MWF with and without Endotoxins. The level of TNF-α in the spleen cell culture obtained from the rats exposed to the MWF with or without Endotoxins increased without changing the levels of IL-1β, IL-4, and INF-γ. The level of Endotoxin-specific IgE in the serum obtained from the rats exposed to the MWF with Endotoxins increased dose-dependently, while the levels of total immunoglobulins (IgG1, IgG2a and IgE) and Endotoxin-specific IgG1 and IgG2a remained unchanged. Accordingly, the current results indicate that lung inflammation can be immediately induced by acute or subacute exposure to an MWF contaminated with Endotoxins, and macrophages would appear to play a role in the induction of inflammation along with B-cell functions rather than T-cell functions, after subacute exposure to an MWF with Endotoxins. In addition, Endotoxin-specific IgE is an early marker for Endotoxin exposure in the workplace.
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inflammatory and immunological responses to subchronic exposure to Endotoxin contaminated metalworking fluid aerosols in f344 rats
Environmental Toxicology, 2005Co-Authors: Il Je Yu, Mingu Kang, Daniel R Marshak, Changkiu Moon, Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Rats were exposed for 6 h per day in inhalation chambers to a 10 mg/m3 concentration of metalworking fluid (MWF) contaminated with Endotoxin at concentrations of 1813 (low dose) and 20,250 eu/m3 (high dose) 5 days per week for 8 weeks. It was found that 94.7% of the MWF aerosol particles had diameters in the range of 0.42–4.6 μm, with geometric mean diameter of 1.56 μm. The body weight and pulmonary function parameters were measured every week during the 8 weeks of exposure, whereas bronchoalveolar lavage (BAL) fluid was prepared to measure the inflammatory markers and cytokines after the 8 weeks of exposure. There were no changes in body weight and respiratory function (tidal volume and respiratory frequency) during the 8 weeks of exposure to the MWF containing Endotoxins, yet lung weight increased significantly (P < 0.05) in the rats exposed to the MWF both with and without Endotoxins. The number of polymorphonuclear (PMN) cells in the BAL fluid increased significantly (P < 0.05) in the rats exposed to MWF with Endotoxins, and the levels of cytokines such as IL-4, INF-γ, IL-1β, and TNF-α also were significantly increased (P < 0.05) compared to the control. The NOx production activity of the BAL cells increased significantly (P < 0.05) in the rats exposed to the MWF with and without Endotoxins. Increases in lung weight, number of PMN cells, and levels of extracellular cytokines and NOx were all more significant in the rats exposed to the MWF with Endotoxins rather than in those exposed to MWF without Endotoxins. In spleen cell cultures, T-cell proliferation activity was decreased, yet cytokine levels (INF-γ, IL-1β, IL-4, and TNF-α) remained unchanged after repeated exposure to MWF with and without Endotoxins. Although the levels of total IgG1, IgG2a, and IgE antibodies in the serum were not changed, the levels of Endotoxin-specific antibodies, including IgG2a and IgE, were increased significantly (P < 0.05) in the rats exposed to Endotoxins, but there was not a significant increase in Endotoxin-specific IgG1. When taken together, the results indicate that lung inflammatory responses can be induced without changing pulmonary function after repeated exposure to MWFs contaminated with Endotoxins. In addition, Endotoxin-specific IgG2a and IgE may be effective biomarkers for workers exposed to MWFs contaminated with Endotoxins in the workplace. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 212–218, 2005.
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inflammatory and immunological responses to subchronic exposure to Endotoxin contaminated metalworking fluid aerosols in f344 rats
Environmental Toxicology, 2005Co-Authors: Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Rats were exposed for 6 h per day in inhalation chambers to a 10 mg/m3 concentration of metalworking fluid (MWF) contaminated with Endotoxin at concentrations of 1813 (low dose) and 20,250 eu/m3 (high dose) 5 days per week for 8 weeks. It was found that 94.7% of the MWF aerosol particles had diameters in the range of 0.42–4.6 μm, with geometric mean diameter of 1.56 μm. The body weight and pulmonary function parameters were measured every week during the 8 weeks of exposure, whereas bronchoalveolar lavage (BAL) fluid was prepared to measure the inflammatory markers and cytokines after the 8 weeks of exposure. There were no changes in body weight and respiratory function (tidal volume and respiratory frequency) during the 8 weeks of exposure to the MWF containing Endotoxins, yet lung weight increased significantly (P < 0.05) in the rats exposed to the MWF both with and without Endotoxins. The number of polymorphonuclear (PMN) cells in the BAL fluid increased significantly (P < 0.05) in the rats exposed to MWF with Endotoxins, and the levels of cytokines such as IL-4, INF-γ, IL-1β, and TNF-α also were significantly increased (P < 0.05) compared to the control. The NOx production activity of the BAL cells increased significantly (P < 0.05) in the rats exposed to the MWF with and without Endotoxins. Increases in lung weight, number of PMN cells, and levels of extracellular cytokines and NOx were all more significant in the rats exposed to the MWF with Endotoxins rather than in those exposed to MWF without Endotoxins. In spleen cell cultures, T-cell proliferation activity was decreased, yet cytokine levels (INF-γ, IL-1β, IL-4, and TNF-α) remained unchanged after repeated exposure to MWF with and without Endotoxins. Although the levels of total IgG1, IgG2a, and IgE antibodies in the serum were not changed, the levels of Endotoxin-specific antibodies, including IgG2a and IgE, were increased significantly (P < 0.05) in the rats exposed to Endotoxins, but there was not a significant increase in Endotoxin-specific IgG1. When taken together, the results indicate that lung inflammatory responses can be induced without changing pulmonary function after repeated exposure to MWFs contaminated with Endotoxins. In addition, Endotoxin-specific IgG2a and IgE may be effective biomarkers for workers exposed to MWFs contaminated with Endotoxins in the workplace. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 212–218, 2005.
Min-gu Kang - One of the best experts on this subject based on the ideXlab platform.
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Respiratory effect of acute and subacute exposure to Endotoxin-contaminated metal working fluid (MWF) aerosols on Sprague-Dawley rats
Archives of Toxicology, 2005Co-Authors: Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Male Sprague-Dawley rats were exposed to a water-soluble metal working fluid (MWF) (5% v/v) contaminated with Endotoxins (10,000 eu/ml or 100,000 eu/ml) at 10 mg/m3 for six hours per day for three days (acute exposure) or two weeks (subacute exposure). The geometric mean diameter of the MWF aerosols was 1.56 μm, and the airborne Endotoxin concentrations ranged from 1,231 to 2,173 eu/m3 (10,000 eu/ml in the bulk MWF) for the low dose and 19,263–27,386 eu/m3 (100,000 eu/ml in the bulk MWF) for the high dose. Minimal effects were observed after exposure to 10 mg/m3 of the MWF without Endotoxins for three days or two weeks. However, an increase in the number of polymorphonuclear cells (PMNs) and the level of protein was noted in the bronchoalveolar lavage (BAL) fluid from the rats acutely exposed to the MWF with Endotoxins. The acute exposure produced a greater increase in the number of PMNs and total cell number in the BAL fluid than the subacute exposure. The number of white blood cells in the peripheral blood and the weight of the lungs both increased after the subacute exposure to the MWF aerosol with Endotoxins, indicating increased vascular permeability in response to the Endotoxin exposure. The levels of cyotokines such as IL-4, INF-γ, and IL-1β in the BAL fluid from the rats exposed to the MWF with or without Endotoxins remained unchanged. Although the level of nitric oxide (NOx) in the BAL supernatant did not show any change, the induction of NOx from the alveolar macrophages increased in the rats acutely or subacutely exposed to the MWF contaminated with Endotoxins. The ConA-induced proliferation response showed no change, yet the LPS-induced proliferation response was significantly increased in the splenocytes from the rats subacutely exposed to the MWF with and without Endotoxins. The level of TNF-α in the spleen cell culture obtained from the rats exposed to the MWF with or without Endotoxins increased without changing the levels of IL-1β, IL-4, and INF-γ. The level of Endotoxin-specific IgE in the serum obtained from the rats exposed to the MWF with Endotoxins increased dose-dependently, while the levels of total immunoglobulins (IgG1, IgG2a and IgE) and Endotoxin-specific IgG1 and IgG2a remained unchanged. Accordingly, the current results indicate that lung inflammation can be immediately induced by acute or subacute exposure to an MWF contaminated with Endotoxins, and macrophages would appear to play a role in the induction of inflammation along with B-cell functions rather than T-cell functions, after subacute exposure to an MWF with Endotoxins. In addition, Endotoxin-specific IgE is an early marker for Endotoxin exposure in the workplace.
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inflammatory and immunological responses to subchronic exposure to Endotoxin contaminated metalworking fluid aerosols in f344 rats
Environmental Toxicology, 2005Co-Authors: Il Je Yu, Mingu Kang, Daniel R Marshak, Changkiu Moon, Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Rats were exposed for 6 h per day in inhalation chambers to a 10 mg/m3 concentration of metalworking fluid (MWF) contaminated with Endotoxin at concentrations of 1813 (low dose) and 20,250 eu/m3 (high dose) 5 days per week for 8 weeks. It was found that 94.7% of the MWF aerosol particles had diameters in the range of 0.42–4.6 μm, with geometric mean diameter of 1.56 μm. The body weight and pulmonary function parameters were measured every week during the 8 weeks of exposure, whereas bronchoalveolar lavage (BAL) fluid was prepared to measure the inflammatory markers and cytokines after the 8 weeks of exposure. There were no changes in body weight and respiratory function (tidal volume and respiratory frequency) during the 8 weeks of exposure to the MWF containing Endotoxins, yet lung weight increased significantly (P < 0.05) in the rats exposed to the MWF both with and without Endotoxins. The number of polymorphonuclear (PMN) cells in the BAL fluid increased significantly (P < 0.05) in the rats exposed to MWF with Endotoxins, and the levels of cytokines such as IL-4, INF-γ, IL-1β, and TNF-α also were significantly increased (P < 0.05) compared to the control. The NOx production activity of the BAL cells increased significantly (P < 0.05) in the rats exposed to the MWF with and without Endotoxins. Increases in lung weight, number of PMN cells, and levels of extracellular cytokines and NOx were all more significant in the rats exposed to the MWF with Endotoxins rather than in those exposed to MWF without Endotoxins. In spleen cell cultures, T-cell proliferation activity was decreased, yet cytokine levels (INF-γ, IL-1β, IL-4, and TNF-α) remained unchanged after repeated exposure to MWF with and without Endotoxins. Although the levels of total IgG1, IgG2a, and IgE antibodies in the serum were not changed, the levels of Endotoxin-specific antibodies, including IgG2a and IgE, were increased significantly (P < 0.05) in the rats exposed to Endotoxins, but there was not a significant increase in Endotoxin-specific IgG1. When taken together, the results indicate that lung inflammatory responses can be induced without changing pulmonary function after repeated exposure to MWFs contaminated with Endotoxins. In addition, Endotoxin-specific IgG2a and IgE may be effective biomarkers for workers exposed to MWFs contaminated with Endotoxins in the workplace. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 212–218, 2005.
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inflammatory and immunological responses to subchronic exposure to Endotoxin contaminated metalworking fluid aerosols in f344 rats
Environmental Toxicology, 2005Co-Authors: Il Je Yu, Min-gu Kang, Daniel R. Marshak, Chang-kiu MoonAbstract:Rats were exposed for 6 h per day in inhalation chambers to a 10 mg/m3 concentration of metalworking fluid (MWF) contaminated with Endotoxin at concentrations of 1813 (low dose) and 20,250 eu/m3 (high dose) 5 days per week for 8 weeks. It was found that 94.7% of the MWF aerosol particles had diameters in the range of 0.42–4.6 μm, with geometric mean diameter of 1.56 μm. The body weight and pulmonary function parameters were measured every week during the 8 weeks of exposure, whereas bronchoalveolar lavage (BAL) fluid was prepared to measure the inflammatory markers and cytokines after the 8 weeks of exposure. There were no changes in body weight and respiratory function (tidal volume and respiratory frequency) during the 8 weeks of exposure to the MWF containing Endotoxins, yet lung weight increased significantly (P < 0.05) in the rats exposed to the MWF both with and without Endotoxins. The number of polymorphonuclear (PMN) cells in the BAL fluid increased significantly (P < 0.05) in the rats exposed to MWF with Endotoxins, and the levels of cytokines such as IL-4, INF-γ, IL-1β, and TNF-α also were significantly increased (P < 0.05) compared to the control. The NOx production activity of the BAL cells increased significantly (P < 0.05) in the rats exposed to the MWF with and without Endotoxins. Increases in lung weight, number of PMN cells, and levels of extracellular cytokines and NOx were all more significant in the rats exposed to the MWF with Endotoxins rather than in those exposed to MWF without Endotoxins. In spleen cell cultures, T-cell proliferation activity was decreased, yet cytokine levels (INF-γ, IL-1β, IL-4, and TNF-α) remained unchanged after repeated exposure to MWF with and without Endotoxins. Although the levels of total IgG1, IgG2a, and IgE antibodies in the serum were not changed, the levels of Endotoxin-specific antibodies, including IgG2a and IgE, were increased significantly (P < 0.05) in the rats exposed to Endotoxins, but there was not a significant increase in Endotoxin-specific IgG1. When taken together, the results indicate that lung inflammatory responses can be induced without changing pulmonary function after repeated exposure to MWFs contaminated with Endotoxins. In addition, Endotoxin-specific IgG2a and IgE may be effective biomarkers for workers exposed to MWFs contaminated with Endotoxins in the workplace. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 212–218, 2005.