Ferruginous components of particulate matters in subway environments, α-Fe2O3 or Fe3O4, exacerbates allergies.

The respiratory effects of particulate matter (PM) in subway station platforms or tunnels have attracted considerable research attention. However, no studies have characterized the effects of subway PM on allergic immune responses. In this study, iron oxide (α-Fe2O3 and Fe3O4) particles-the main components of subway PM-were intratracheally administered to BALB/c mice where ovalbumin (OVA) induced allergic pulmonary inflammation. Iron oxide particles enhanced OVA-induced eosinophil recruitment around the bronchi and mucus production from airway epithelium. The concentrations of type 2 cytokines, namely, interleukin (IL)-5 and IL-13, in bronchial alveolar lavage fluids were increased by iron oxide particles. Iron oxide particles also increased the number of type 2 innate lymphoid cells and CD86+ cells in the lung. Moreover, phagocytosis of particles in lung cells was confirmed by Raman spectroscopy. In a subsequent in vitro study, bone marrow-derived antigen-presenting cells (APCs) isolated from NC/Nga mice were exposed to iron oxide particles and OVA. They were also exposed to outdoor ambient PM: Vehicle Exhaust Particulates (VEP) and Urban Aerosols (UA) as references. Iron oxide particles promoted the release of lactate dehydrogenase, C-X-C motif chemokine ligand 1 and IL-1α from APCs, which tended to be stronger than those of VEP. These results suggest that iron oxide particles enhance antigen presentation in the lungs, promoting allergic immune response in mice; iron oxide particles-induced death and inflammatory response of APCs can contribute to allergy exacerbation. Although iron oxide particles do not contain various compounds like VEP, iron oxide alone may have sufficient influence.

Cardiac Arrest Following Remimazolam-Induced Anaphylaxis: A Case Report.

Remimazolam is a recently approved benzodiazepine sedative. We report a case of a 72-year-old man who experienced a cardiac arrest due to severe anaphylaxis immediately after general anesthesia induction. Based on the results of skin tests, including those for dextran 40, an excipient in the remimazolam solution, and a review of drugs given during 3 anesthetics, remimazolam was identified as the probable causative agent. Although remimazolam is structurally similar to midazolam, the patient was not allergic to midazolam as demonstrated before and after anaphylaxis. This report highlights the potential risk of allergic reactions to remimazolam.

Di-(2-ethylhexyl) phthalate enhances cytokine release from group 2 innate lymphoid cells in the presence of interleukin-33.

Epidemiological and experimental studies have shown that di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, can aggravate allergic diseases. DEHP promotes adaptive immune responses, although its effect on the innate immune system remains largely unknown. The present study investigated the effects of DEHP on group 2 innate lymphoid cells (ILC2) that produce Th2 cytokines in response to epithelial cell-derived cytokines, such as interleukin (IL)-33. ILC2 (lineage-negative, CD45.2+, Sca1+, KLRG1+) were isolated from the lungs of C57BL/6 J mice. Co-exposure to DEHP and IL-33 significantly increased IL-5 release from ILC2, whose level was higher than that of the vehicle and IL-33 alone. The effects of DEHP in the presence of IL-33 showed an inverted-U dose-response. The present is the first report showing that DEHP exacerbates allergy through the innate immune system.

Role of necroptosis of alveolar macrophages in acute lung inflammation of mice exposed to titanium dioxide nanoparticles.

Titanium dioxide (TiO2) nanoparticles are indispensable for daily life but induce acute inflammation, mainly via inhalation exposure. TiO2 nanoparticles can be phagocytosed by alveolar macrophages (AMs) in vivo and cause necroptosis of exposed cells in vitro. However, the relationship between localization of TiO2 nanoparticles in the lungs after exposure and their biological responses including cell death and inflammation remains unclear. This study was conducted to investigate the intra/extracellular localization of TiO2 nanoparticles in murine lungs at 24 h after intratracheal exposure to rutile TiO2 nanoparticles and subsequent local biological reactions, specifically necroptosis of AMs and lung inflammation. We found that TiO2 exposure induced leukocyte migration into the alveolar region and increased the secretion of C-C motif ligand (CCL) 3 in the bronchoalveolar lavage (BAL) fluid. A combination of Raman spectroscopy and staining of cell and tissue samples confirmed that AMs phagocytose TiO2. AMs that phagocytosed TiO2 nanoparticles showed necroptosis, characterized by the expression of phosphorylated mixed lineage kinase domain-like protein and translocation of high mobility group box-1 from the cell nucleus to the cytoplasm. In primary cultured AMs, TiO2 also induced necroptosis and increased the secretion of CCL3. Necroptosis inhibitors suppressed the increase in CCL3 secretion in both the BAL fluid and culture supernatant of AMs and suppressed the increase in leukocytes in the BAL fluid. These data suggest that necroptosis of AMs that phagocytose TiO2 nanoparticles is involved as part of the mechanism by which TiO2 induces acute lung inflammation.

PM2.5 collected using cyclonic separation causes stronger biological responses than that collected using a conventional filtration method.

Evaluation of the health effects of particulate matter with aerodynamic dias. ≤ 2.5 µm (PM2.5) should reflect realistic condition in ambient atmosphere. However, using conventional filtration methods, only extracts from PM2.5 collected on the filter can be analyzed and not the particle itself. Cyclonic separation is a technique that enables the direct analysis of the effects of the crude "powder form" of PM2.5 on respiratory health. Airway epithelial cells and antigen-presenting cells were exposed to PM2.5 collected during the same period using a conventional filtration method or cyclonic separation. PM2.5 collected using cyclonic separation led to a higher secretion of interleukins 6 and 8 (IL-6, IL-8) from airway epithelial cells, and IL-6, IL-1ß, tumor necrosis factor-α (TNF-α) secretion, cluster of differentiation 86 (CD86), and dendritic and epithelial cells 205 (DEC205) expression on antigen-presenting cells, compared with the effects of filter-collected PM2.5. Furthermore, PM2.5 collected using cyclonic separation increased inflammatory cytokine levels and induced lung inflammation in vivo. These results suggest that crude PM2.5 collected using cyclonic separation causes stronger biological responses than filter-collected PM2.5. Hence, PM2.5 collected using cyclonic separation can be utilized for a reliable evaluation of the health effects of ambient PM2.5.