Tag: induction

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Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.

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Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.

Toxicol Appl Pharmacol. 2015 Jun 11;

Authors: Broström JM, Ye ZW, Axmon A, Littorin M, Tinnerberg H, Lindh CH, Zheng H, Ghalali A, Stenius U, Jönsson BA, Högberg J

Abstract
Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of TDI on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of toluene diisocyanate (TDI) exposure in urine collected from workers exposed to<5p.p.b.(parts per billion). Information on workers’ symptoms was collected through interviews. One nM TDI robustly induced ATX release within 10min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose-response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting “sneezing”, the LPA levels were higher than among non-symptomatic workers. This is a first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity.

PMID: 26072274 [PubMed – as supplied by publisher]

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Programmed cell death ligand 2 regulates T(H)9 differentiation and induction of chronic airway hyperreactivity.

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Programmed cell death ligand 2 regulates T(H)9 differentiation and induction of chronic airway hyperreactivity.

J Allergy Clin Immunol. 2012 Nov 19;

Authors: Kerzerho J, Maazi H, Speak AO, Szely N, Lombardi V, Khoo B, Geryak S, Lam J, Soroosh P, Van Snick J, Akbari O

Abstract
BACKGROUND: Asthma is defined as a chronic inflammatory disease of the airways; however, the underlying physiologic and immunologic processes are not fully understood. OBJECTIVE: The aim of this study was to determine whether T(H)9 cells develop in vivo in a model of chronic airway hyperreactivity (AHR) and what factors control this development. METHOD: We have developed a novel chronic allergen exposure model using the clinically relevant antigen Aspergillus fumigatus to determine the time kinetics of T(H)9 development in vivo. RESULTS: T(H)9 cells were detectable in the lungs after chronic allergen exposure. The number of T(H)9 cells directly correlated with the severity of AHR, and anti-IL-9 treatment decreased airway inflammation. Moreover, we have identified programmed cell death ligand (PD-L) 2 as a negative regulator of T(H)9 cell differentiation. Lack of PD-L2 was associated with significantly increased TGF-? and IL-1? levels in the lungs, enhanced pulmonary T(H)9 differentiation, and higher morbidity in the sensitized mice. CONCLUSION: Our findings suggest that PD-L2 plays a pivotal role in the regulation of T(H)9 cell development in chronic AHR, providing novel strategies for modulating adaptive immunity during chronic allergic responses.

PMID: 23174661 [PubMed – as supplied by publisher]

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[Live-threatening bronchospasm during anesthesia induction : When pure routine becomes a nightmare.]

[Live-threatening bronchospasm during anesthesia induction : When pure routine becomes a nightmare.]

Anaesthesist. 2011 Sep 16;

Authors: Rüggeberg A, Breckwoldt J

Abstract
This article reports a case of live-threatening respiratory failure during induction of anesthesia. An 18-year-old female was admitted to hospital for an axillary abscess incision on a public holiday. The patient had a history of asthmatic episodes and an allergy to milk protein and 2 years previously an asthmatic attack had possibly been treated by mechanical ventilation. Retrospectively, this event turned out to be a cardiac arrest with mechanical ventilation for 24 h. During induction of anesthesia the patient suddenly developed massive bronchospasms and ventilation was impossible for minutes. Oxygen saturation fell below 80% over a period of 12 min with a lowest measurement of 13%. The patient was treated with epinephrine, prednisolone, antihistamine drugs, ß(2)-agonists, s-ketamine and methylxanthines and 15 min later the oxygen saturation returned to normal values. After mild therapeutic hypothermia for 24 h mechanical ventilation was still required for another 4 days. The patient recovered completely and was discharged home on day 19. Initially propofol was suspected of having caused an anaphylactic shock but in retrospect, the diagnosis of near fatal asthma was more likely. The onset of the event was facilitated by the patient playing down the history of asthmatic episodes due to a strong wish for independency and negation of the severity of the disease.

PMID: 21918825 [PubMed – as supplied by publisher]

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