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Mechanisms of Lung Inflammation Following Exposure to Swine Barn AirCharavaryamath, Chandrashekhar 04 September 2008
Occupational exposure to endotoxin-rich swine barn air induces respiratory diseases and loss of lung function. Barn exposure induces recruitment of pulmonary intravascular monocytes/macrophages (PIMMs) and subsequent increased host sensitivity to <i>Escherichia coli</i> LPS challenge. Therefore, to further clarify the biology of PIMMs we examined the role of recruited PIMMs in a rat <i>Escherichia coli</i>-induced lung inflammation model. Following sepsis, lung inflammation was induced with recruitment of PIMMs and subsequently, <i>Escherichia coli</i> LPS challenge exacerbated the lung inflammation with localization of multiple inflammatory cytokines in PIMMs to suggest their possible involvement in modulating lung inflammation in this model.<p>
In order to delineate mechanisms of barn air induced lung dysfunction, a rat model of occupational exposure was characterized to show that one and five exposures to the barn environment induced acute lung inflammation and increased airway hyperresponsiveness (AHR). Following 20 exposures, AHR was dampened to indicate adaptive responses. Barn air contains high levels of endotoxin which led us to investigate its role in lung inflammation and AHR. Exposure of mice with either a functional TLR4 (WT) or non-functional TLR4 (mutants) to barn air revealed dependence of lung inflammation but not AHR on a functional TLR4.<p>
I investigated whether exposure to barn air alters host responses to a subsequent microbial challenge. Following one day barn exposure and <i>Escherichia coli</i> LPS challenge, lung inflammation was exacerbated with increased granulocytes and IL-1β levels compared to one day barn exposed rats without <i>Escherichia coli</i> LPS challenge. However, increased granulocytes and IL-1β levels in barn exposed and <i>Escherichia coli</i> LPS challenged rats were not different from control rats treated with <i>Escherichia coli</i> LPS indicating a lack of priming effect of barn exposure. However, above results are suggestive of an underlying risk of increased lung inflammation following secondary microbial infection in naïve barn workers.<p>
Lastly, I investigated the expression and activity of novel signalling molecules called <i>N</i>-myristoyltransferase and calcineurin in barn air and <i>E. coli</i> LPS induced lung inflammation models. Following one day barn exposure, increased protein expression but not activity of <i>N</i>-myristoyltransferase and calcineurin was shown. However, there is a need to identify the specific role of these two molecules in barn air induced lung inflammation. To conclude, animal models of barn exposure are useful tools to understand mechanisms of lung inflammation and AHR. However, there is still a need to examine endotoxin-independent nature of AHR and roles of other molecules of the innate immune system in regulating barn air induced effects.
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Mechanisms of Lung Inflammation Following Exposure to Swine Barn AirCharavaryamath, Chandrashekhar 04 September 2008 (has links)
Occupational exposure to endotoxin-rich swine barn air induces respiratory diseases and loss of lung function. Barn exposure induces recruitment of pulmonary intravascular monocytes/macrophages (PIMMs) and subsequent increased host sensitivity to <i>Escherichia coli</i> LPS challenge. Therefore, to further clarify the biology of PIMMs we examined the role of recruited PIMMs in a rat <i>Escherichia coli</i>-induced lung inflammation model. Following sepsis, lung inflammation was induced with recruitment of PIMMs and subsequently, <i>Escherichia coli</i> LPS challenge exacerbated the lung inflammation with localization of multiple inflammatory cytokines in PIMMs to suggest their possible involvement in modulating lung inflammation in this model.<p>
In order to delineate mechanisms of barn air induced lung dysfunction, a rat model of occupational exposure was characterized to show that one and five exposures to the barn environment induced acute lung inflammation and increased airway hyperresponsiveness (AHR). Following 20 exposures, AHR was dampened to indicate adaptive responses. Barn air contains high levels of endotoxin which led us to investigate its role in lung inflammation and AHR. Exposure of mice with either a functional TLR4 (WT) or non-functional TLR4 (mutants) to barn air revealed dependence of lung inflammation but not AHR on a functional TLR4.<p>
I investigated whether exposure to barn air alters host responses to a subsequent microbial challenge. Following one day barn exposure and <i>Escherichia coli</i> LPS challenge, lung inflammation was exacerbated with increased granulocytes and IL-1β levels compared to one day barn exposed rats without <i>Escherichia coli</i> LPS challenge. However, increased granulocytes and IL-1β levels in barn exposed and <i>Escherichia coli</i> LPS challenged rats were not different from control rats treated with <i>Escherichia coli</i> LPS indicating a lack of priming effect of barn exposure. However, above results are suggestive of an underlying risk of increased lung inflammation following secondary microbial infection in naïve barn workers.<p>
Lastly, I investigated the expression and activity of novel signalling molecules called <i>N</i>-myristoyltransferase and calcineurin in barn air and <i>E. coli</i> LPS induced lung inflammation models. Following one day barn exposure, increased protein expression but not activity of <i>N</i>-myristoyltransferase and calcineurin was shown. However, there is a need to identify the specific role of these two molecules in barn air induced lung inflammation. To conclude, animal models of barn exposure are useful tools to understand mechanisms of lung inflammation and AHR. However, there is still a need to examine endotoxin-independent nature of AHR and roles of other molecules of the innate immune system in regulating barn air induced effects.
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A role for toll-like receptor-4 in pulmonary angiogenesis following multiple exposures to swine barn airJuneau, Vanessa Jade 14 June 2007
Swine barn air is a heterogeneous mixture of dust, bacteria and irritant chemicals including ammonia and hydrogen sulphide. Gram-negative bacteria are commonly found in swine barn air and significantly contribute to pulmonary disease in unprotected swine barn workers, through the endotoxin moiety, lipopolysaccharide (LPS). Toll-like Receptor-4 is the ligand for LPS. It is found on many cell types including monocytes, macrophages, neutrophils, endothelial cells, and to a lesser extent, epithelial cells. The severity and outcome of acute lung injury following barn air exposures depends upon the balance between epithelial and vascular endothelial repair mechanisms, including angiogenesis. Vascular Endothelial Growth Factor (VEGF) is an endothelial mitogen produced by mesenchymal and alveolar Type II epithelial cells and by activated bronchial airway epithelial cells. Research investigating the role of cytokines in angiogenesis has shown that close proximity of immune cells and endothelial cells modulates the production of various compounds that regulate vascular function. Given that LPS is the ligand for TLR4 there appeared to be a role for TLR4 in angiogenesis, particularly following endotoxin exposure. To determine whether this was occurring, we examined whether exposure to swine barn air alters vascular density in the lungs and the role of TLR4 using a murine model. Toll-like Receptor-4 wild-type (C3HeB/FeJ) and TLR4 mutant (C3H/HeJ) mice were obtained and exposed to swine barn air for 1-, 5-, or 20-days for 8 hours/day. Wild-type animals showed a 127% increase in vascular density after 20-days barn air exposure. Vascular Endothelial Growth Factor-A protein levels were decreased by 0.62-fold after one-day swine barn air exposure in wild-type animals, indicating that VEGF-A is being used as a pro-angiogenic mitogen. Transcription of VEGF-A mRNA was increased in wild-type animals after all swine barn air exposure periods. The receptor VEGFR-1 showed increased mRNA transcription over all time points. These effects were only observed in TLR4 wild-type animals, indicating that these effects are mediated by TLR4. Further, VEGF-A and VEGFR-1 appear to be involved in the manifestation of TLR4-induced angiogenesis in the lung.
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A role for toll-like receptor-4 in pulmonary angiogenesis following multiple exposures to swine barn airJuneau, Vanessa Jade 14 June 2007 (has links)
Swine barn air is a heterogeneous mixture of dust, bacteria and irritant chemicals including ammonia and hydrogen sulphide. Gram-negative bacteria are commonly found in swine barn air and significantly contribute to pulmonary disease in unprotected swine barn workers, through the endotoxin moiety, lipopolysaccharide (LPS). Toll-like Receptor-4 is the ligand for LPS. It is found on many cell types including monocytes, macrophages, neutrophils, endothelial cells, and to a lesser extent, epithelial cells. The severity and outcome of acute lung injury following barn air exposures depends upon the balance between epithelial and vascular endothelial repair mechanisms, including angiogenesis. Vascular Endothelial Growth Factor (VEGF) is an endothelial mitogen produced by mesenchymal and alveolar Type II epithelial cells and by activated bronchial airway epithelial cells. Research investigating the role of cytokines in angiogenesis has shown that close proximity of immune cells and endothelial cells modulates the production of various compounds that regulate vascular function. Given that LPS is the ligand for TLR4 there appeared to be a role for TLR4 in angiogenesis, particularly following endotoxin exposure. To determine whether this was occurring, we examined whether exposure to swine barn air alters vascular density in the lungs and the role of TLR4 using a murine model. Toll-like Receptor-4 wild-type (C3HeB/FeJ) and TLR4 mutant (C3H/HeJ) mice were obtained and exposed to swine barn air for 1-, 5-, or 20-days for 8 hours/day. Wild-type animals showed a 127% increase in vascular density after 20-days barn air exposure. Vascular Endothelial Growth Factor-A protein levels were decreased by 0.62-fold after one-day swine barn air exposure in wild-type animals, indicating that VEGF-A is being used as a pro-angiogenic mitogen. Transcription of VEGF-A mRNA was increased in wild-type animals after all swine barn air exposure periods. The receptor VEGFR-1 showed increased mRNA transcription over all time points. These effects were only observed in TLR4 wild-type animals, indicating that these effects are mediated by TLR4. Further, VEGF-A and VEGFR-1 appear to be involved in the manifestation of TLR4-induced angiogenesis in the lung.
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Analyse und Bewertung von Parametern der Produktionsumwelt bei der Milchgewinnung mit automatischen Melksystemen (AMS)Unrath, Jens 23 February 2005 (has links)
Automatische Melksysteme (AMS) gelten als jüngste Innovation auf dem Gebiet der Melktechnik und weisen im Vergleich mit konventionellen Melkständen eine Reihe von Besonderheiten auf. Um die Kühe zum freiwilligen und regelmäßigen Besuch des Melksystems anzuhalten, sind optimale mikroklimatische Bedingungen in der Melkbox notwendig. Die Analyse der mikroklimatischen Bedingungen in AMS erfolgte in einem Betrieb mit zwei parallel arbeitenden AMS und 110 melkenden Kühen. Dabei wurden die Parameter Luftqualität in der Melkbox und im Stall, Geräuschbelastung innerhalb der Melkbox während des Melkens sowie Verschmutzungsgrad und Keimgehalt an relevanten Punkten des AMS untersucht. Um die jahreszeitlichen Einflüsse auf das Stallklima zu kennzeichnen erfolgten die Untersuchungen im März 2002, Juni 2002 sowie Januar 2003. Eine besondere mikroklimatische Situation in der Melkbox konnte in den Analysen für die Stallluftparameter Kohlendioxid und Methan festgestellt werden. Dabei wurden erhöhte Konzentrationen immer dann beobachtet, wenn sich eine Kuh in der Melkbox befand. Die Bauweise des AMS im Kopfbereich der Melkbox konnte als entscheidender Grund für die hohen Konzentrationen der Gase ermittelt werden, da dadurch der Luftaustausch mit der Umgebung behindert wird. Die Geräuschkulisse für die Kühe innerhalb der Melkbox erwies sich während der Eutervorbereitung als besonders belastend, da der Schallpegel hier am höchsten war und gleichzeitig eine Frequenzverschiebung in den höherfrequenten Bereich festzustellen war. Ein erster Ansatz der Beschreibung der hygienischen Zustände in einem AMS erfolgte mit Hilfe von digitalen Bildern, welche an den Schnittstellen zwischen Tier, Endprodukt und Technik gemacht wurden. Der visuell wahrnehmbare Verschmutzungsgrad ließ sich in Beziehung zu gleichzeitig erfassten Tupferproben und darin isolierten Keimen setzen. Eine Verbesserung bzw. Anpassung der mikroklimatischen Situation innerhalb von AMS erscheint als notwendig, um eine ausreichende Motivation der Kühe zum Besuch der Melkbox zu erreichen. / Automatic milking systems (AMS) are considered as the most recent innovation in the area of milking technology. In comparison with conventional milking parlour they show a set of specific characteristics. Optimal microclimatic conditions in the milking box are necessary to motivate the cows to visit the milking system voluntarily and regularly. The analysis of the microclimatic conditions in AMS took place on a farm with two AMS working parallel and 110 lactating cows. The parameters examined were: the air quality in the milking box and in the barn, the noise load within the milking box during milking as well as the degree of pollution and the germ load at relevant points of the AMS. To mark the seasonal influences on the climate within the barn, the investigations took place in March 2002, June 2002 as well as January 2003. A special microclimatic situation in the milking box was noticed in the analyses for the barn air parameters carbon dioxide and methane. Whenever a cow was in the milking box, increased concentrations were observed. The construction method of the AMS in the head area of the milking box was determined as main reason for the high concentrations of gases, since this impedes the interchange of air with the environment. The sound load for the cows within the milking box was particularly heavy during the preparation of the udder. The sound level was highest during the cleaning of the udder and the frequencies shifted into the higher range. The description of the hygienic conditions in an AMS was first approached by means of digital pictures, which were made at the interfaces between animal, final product and technology. The visually perceptible degree of pollution could be set in relation to Dab RPR, which were taken at the same time like the digital pictures, and isolated germs therein. An improvement and/or an adjustment of the microclimatic situation within AMS appears necessary in order to achieve a sufficient motivation of the cows to go into the milking box.
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