Multi-Walled Carbon Nanotubes Augment Allergic Airway Eosinophilic Inflammation by Promoting Cysteinyl Leukotriene Production.

Multi-walled carbon nanotubes (MWCNT) have been reported to promote lung inflammation and fibrosis. The commercial demand for nanoparticle-based materials has expanded rapidly and as demand for nanomaterials grows, so does the urgency of establishing an appreciation of the degree of health risk associated with their increased production and exposure. In this study, we examined whether MWCNT inhalation elicited pulmonary eosinophilic inflammation and influenced the development of allergic airway inflammatory responses.

Prenatal tobacco smoke exposure predisposes offspring mice to exacerbated allergic airway inflammation associated with altered innate effector function.

Background: Epidemiological studies suggest that prenatal and early life environmental exposures have adverse effects on pulmonary function and are important contributors in the development of childhood asthma and allergic disease. The mechanism by which environmental tobacco smoke (ETS) exposure in utero promotes the development of allergic asthma remains unclear. In this study, we investigated the immunological consequences of prenatal exposure to ETS in order to understand events responsible for the development or exacerbation of allergic asthma.

Prenatal environmental tobacco smoke exposure increases allergic asthma risk with methylation changes in mice.

Allergic asthma remains an inadequately understood disease. In utero exposure to environmental tobacco smoke (ETS) has been identified as an environmental exposure that can increase an individual's asthma risk. To improve our understanding of asthma onset and development, we examined the effect of in utero ETS exposure on allergic disease susceptibility in an asthmatic phenotype using a house dust mite (HDM) allergen-induced murine model.

PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust Mite Allergen.

In allergic asthma, inhalation of airborne allergens such as the house dust mite (HDM) effectively activates both innate and adaptive immunity in the lung mucosa. To determine the role of the eicosanoid PGI and its receptor IP during allergic airway sensitization, HDM responses in mice lacking a functional IP receptor (i.e.

S-nitrosoglutathione reductase inhibition regulates allergen-induced lung inflammation and airway hyperreactivity.

Allergic asthma is characterized by Th2 type inflammation, leading to airway hyperresponsivenes, mucus hypersecretion and tissue remodeling. S-Nitrosoglutathione reductase (GSNOR) is an alcohol dehydrogenase involved in the regulation of intracellular levels of S-nitrosothiols. GSNOR activity has been shown to be elevated in human asthmatic lungs, resulting in diminished S-nitrosothiols and thus contributing to increased airway hyperreactivity.

Prostaglandin I₂promotes the development of IL-17-producing γδ T cells that associate with the epithelium during allergic lung inflammation.

γδ T cells rapidly produce cytokines and represent a first line of defense against microbes and other environmental insults at mucosal tissues and are thus thought to play a local immunoregulatory role. We show that allergic airway inflammation was associated with an increase in innate IL-17-producing γδ T (γδ-17) cells that expressed the αEβ7 integrin and were closely associated with the airway epithelium. Importantly, PGI(2) and its receptor IP, which downregulated airway eosinophilic inflammation, promoted the emergence of these intraepithelial γδ-17 cells into the airways by enhancing IL-6 production by lung eosinophils and dendritic cells.

Design and evaluation of a novel fluorescent CB2 ligand as probe for receptor visualization in immune cells.

Cannabinoid CB2 receptor has emerged as a very promising target over the last decades. We have synthesized and evaluated a new fluorescent probe designated NMP6 based on 6-methoxyisatin scaffold, which exhibited selectivity and K(i) value at hCB2 of 387 nM. We have demonstrated its ability to be an effective probe for visualization of CB2 receptor binding using confocal microscopy and a flow cytometry probe for the analysis of CB2 protein expression.

Natural Foxp3(+) regulatory T cells inhibit Th2 polarization but are biased toward suppression of Th17-driven lung inflammation.

nTregs prevent autoimmunity and modulate immune and inflammatory responses to foreign antigens. CD4(+)Foxp3(+) nTregs from DO11.10 mice were expanded ex vivo, and their effectiveness in suppressing the development of lung inflammatory responses, elicited by differentiated CD4(+) T cells following antigen inhalation, was examined.

Antigen-specific Treg regulate Th17-mediated lung neutrophilic inflammation, B-cell recruitment and polymeric IgA and IgM levels in the airways.

Th17 cells play key roles in mediating autoimmunity, inflammation and mucosal host defense against pathogens. To determine whether naturally occurring Treg (nTreg) limit Th17-mediated pulmonary inflammation, OVA-specific CD4+ Th17 cells and expanded CD4+CD25+Foxp3+ nTreg were cotransferred into BALB/c mice that were then exposed to OVA aerosols. Th17 cells, when transferred alone, accumulated in the lungs and posterior mediastinal LN and evoked a pronounced airway hyperreactivity and neutrophilic inflammation, characterized by B-cell recruitment and elevated IgA and IgM levels.

Cutting edge: lung mucosal Th17-mediated responses induce polymeric Ig receptor expression by the airway epithelium and elevate secretory IgA levels.

Polymeric Ig receptor (pIgR) is a central player in mucosal immunity that mediates the delivery of polymeric IgA and IgM to the apical surface of epithelial cells via transcytosis. Emerging evidence suggests that Th17 cells not only mediate autoimmunity but also play key roles in mucosal host defense against pathogens. We demonstrate that OVA-specific CD4(+) Th17 cells, in addition to causing neutrophilic inflammation in mice, mediated a pronounced influx of CD19(+) B cells into the lungs following Ag inhalation.

Likelihood ratios reporting in a tertiary hospital emergency department; a pilot study.

The Emergency Department and the laboratory of our institution jointly developed simple Clinical Pathways for some important clinical conditions (pulmonary embolism, acute myocardial infarction, bile-pancreatic disease) and since May 2004 the positive and negative likelihood ratios have been added to the reports of the tests included in the clinical pathways. In the first semester 30% of clinicians adopted the new mode of tests requesting AMI, Pulmonary embolism and bile pancreatic clinical pathways, respectively, 24% 32% and 42%. According to a survey carried out in 2004 all the ED staff had knowledge of the project.

Prostaglandin I2-IP signaling blocks allergic pulmonary inflammation by preventing recruitment of CD4+ Th2 cells into the airways in a mouse model of asthma.

PGI(2) plays a key role in limiting Th2-mediated airway inflammation. In studies to investigate the mechanism underlying such regulation, we found that the PGI(2) receptor, IP, is preferentially expressed by effector CD4(+) Th2 cells, when compared with Th1 cells. Adoptive transfer of DO11.