Metalworking Fluid with Mycobacteria and Endotoxin Induces Hypersensitivity Pneumonitis in Mice

Thorne, Peter S.; Adamcakova‐Dodd, Andrea; Kelly, Kevin M.; O'Neill, Marsha E.; Duchaine, Caroline

doi:10.1164/rccm.200405-627oc

Cited by 63 publications

(51 citation statements)

References 49 publications

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“…Inflammatory responses to inhaled endotoxin have been studied in both humans (2,(32)(33)(34) and mice (35)(36)(37)(38). In general, inhalation or nasal aspiration of endotoxin by mice induces similar host responses and changes (35,39), and these reflect human airway responsiveness (33).…”

Section: Discussionmentioning

confidence: 99%

MD-2–Dependent Pulmonary Immune Responses to Inhaled Lipooligosaccharides

Hađina¹,

Weiss²,

McCray³

et al. 2008

Am J Respir Cell Mol Biol

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Endotoxins represent one of the most potent classes of microbial immunoactive components that can cause pulmonary inflammation. The aim of this study was to compare the inflammatory potency of two types of Neisseria meningitidis endotoxins (lipooligosaccharides) in lungs: wild type (hexaacylated, LOS wt ) and mutant type (pentaacylated, LOS msbB ), and to determine the importance of MD-2 in endotoxin responses in lungs in vivo. Endotoxin-normoresponsive mice (BALB/c) were exposed to selected doses of penta-and hexaacylated lipooligosaccharides (LOS) by nasal aspiration. Cellular and cytokine/chemokine inflammatory responses in bronchoalveolar lavage were measured at 1-, 4-, 8-, 16-, 24-, and 48-hour time points. MD-2-null mice were exposed to one dose of hexaacylated LOS and inflammatory responses were measured after 4 and 24 hours. Inhalation of hexaacylated LOS resulted in strong inflammatory responses, while pentaacylated LOS was much less potent in inducing increases of neutrophils, TNF-a, macrophage inflammatory protein-1a, IL-6, granulocyte colony-stimulating factor, and IL-1b concentration in bronchoalveolar lavage. Similar kinetics of inflammatory responses in lungs were found in both types of endotoxin exposures. Inhalation of hexaacylated LOS in MD-2-null mice resulted in significantly lower numbers of neutrophils in bronchoalveolar lavage than in normoresponsive mice. Markedly lower inflammatory potency of pentaacylated LOS was observed compared with hexaacylated LOS. Hyporesponsiveness in MD-2-null mice after nasal aspiration of wild-type LOS indicate its essential role in airway responsiveness to endotoxin.

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Section: Discussionmentioning

confidence: 99%

MD-2–Dependent Pulmonary Immune Responses to Inhaled Lipooligosaccharides

Hađina¹,

Weiss²,

McCray³

et al. 2008

Am J Respir Cell Mol Biol

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“…was in fact the mycobacteria present (Khan et al, 2005). Furthermore, M.immunogenum was consistently identified in MWF in studies from the USA, and parts of Europe and thus implicated as a possible causative factor (Veilette et al, 2004;Thorne et al, 2006).…”

Section: Mycobacterial Contaminationmentioning

confidence: 99%

“…Supportive evidence was obtained from both human epidemiological and animal exposure studies. Using a murine model, Thorne et al, (2006) This study was conducted with lysed and heat killed M.immunogenum. However, it is unclear whether mycobacteria within MWF are viable due to their resilience to biocides and disinfectants.…”

Section: Mycobacterial Contaminationmentioning

confidence: 99%

“…A single bacterial cell can contain ~2 million LPS molecules per cell. The increased mobility of endotoxins, in addition to their small size increases their surface area, thus making them readily inhalable (Thorne et al, 2006). Moreover, they can instigate biological effects at concentrations above 90 EU/m 3 in some humans; these levels are approximately equivalent to 9 endotoxins /m 3 (Value taken from the Health Council of Netherlands (DECOS).…”

Section: Biofouling and Endotoxinsmentioning

confidence: 99%

“…These include; chemicals such boron (MHDS95/3), or biological contaminants such as bacteria, fungi (Perkins and Angenent, 2010) and endotoxins (Thorne et al, 2006). However, it is now understood sampling biological components requires much more consideration when correlating results to MWF sump samples.…”

Section: Air Sampling Techniquesmentioning

confidence: 99%

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