intranasally with ragweed pollen extract (RWPE) or cat dander extract. (CDE), and innate and allergic inflammation were quantified. WT RAW and Sting KO RAW ...
AB264 Abstracts
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Expression of Lipoxin A4 Receptor: FPRL1 in Human Nasal Mucosa
Hideaki Shirasaki, Etsuko Saikawa, and Tetsuo Himi, MD, PhD; Sapporo Medical University, Sapporo, Japan. RATIONALE: Lipoxins(LXs) are a group of lipoxygenase derived eicosanoids which in contrast to other eicosanoids including leukotrienes, are recognized to have potent anti-inflammatory and pro-resolution properties. Formyl peptide receptor-like receptor 1(FPRL1) also called also called LXA4 receptor, functions as a component of the inflammatory response. To date, only a few reports have shown the existence of this receptor in the airway. The purpose of this study was to investigate the expression and the localization of FPRL1 protein in human nasal mucosa by western blotting and immunohistochemical analysis. METHODS: Human turbinates were obtained after turbinectomy from 6 patients with nasal obstruction refractory to medical therapy. The expressionof FPRL1 protein was evaluated by western blotting. To identify the cells expressing FPRL1 protein, immunostaining was performed using anti-human FPRL1 antibody. RESULTS: A single band of approximately 38kDa was detected in human turbinates and primary cultured nasal epithelial cells by western blot analysis using anti-FPRL1 antibody. The immunohistochemical studies revealed that anti-FPRL1 antibody mainly labeled epithelial cells, submucosal glands and some inflammatory leukocytes in nasal mucosa. CONCLUSIONS: These results may have an important clinical implication for understanding the role of LXA4 receptor on upper airway diseases such as allergic rhinitis and non-allergic rhinitis.
829
Sting Regulates Innate and Allergic Airway Inflammation
MONDAY
Koa Hosoki, MD, Toshiko Itazawa, MD, PhD, Istvan Boldogh, and Sanjiv Sur, MD; University of Texas Medical Branch, Galveston, TX. RATIONALE: Exposure of airway epithelial cells to ragweed pollen induces DNA damage and base-excision repair. Sting is an intracellular receptor that senses cytosolic and damaged DNA. However, the role of Sting in allergic airway inflammation has not been elucidated. METHODS: Wild-type (WT) mice and Sting KO mice were challenged intranasally with ragweed pollen extract (RWPE) or cat dander extract (CDE), and innate and allergic inflammation were quantified. WT RAW and Sting KO RAW cells were stimulated with diverse allergenic extracts, and interferon regulatory factor (IRF) 3,7,9 reporter activity was quantified. RESULTS: A single RWPE or CDE intranasal challenge in na€ıve WT mice stimulated neutrophil recruitment into the airways. Compared to WT mice, in Sting KO mice both RWPE (52% reduction) and CDE (75% reduction) induced reduced neutrophil recruitment. Repeated-challenge with RWPE or CDE in WT mice induced allergic inflammation, characterized by recruitment of eosinophils in BALF and levels of total IgE and antigen-specific IgE in serum. Compared to WT mice, in Sting KO mice both RWPE (45% reduction) and CDE (55% reduction) induced reduced eosinophil recruitment and total IgE and antigen-specific IgE in serum. RWPE, firebush, pigweed, CDE, and house dust mite extract induced Sting-dependent IRF activation in RAW cells by 60-87%. CONCLUSIONS: Sting mediates RWPE and CDE-induced innate and allergic inflammation in the lungs. Sting stimulates RWPE, firebush, pigweed, CDE, and house dust mite extract induced IRF activation in cells. Our data suggest that sensing of damaged DNA in cytosol by Sting may play a role in allergen-induced innate and allergic inflammation.
J ALLERGY CLIN IMMUNOL FEBRUARY 2017
830
Expression of Nasal Epithelial Platelet Activating Factor Receptor (PAFR) and in vivo Exposure to Air Pollution
Lisa Miyashita, Michele Padovan, Reetika Suri, Abigail Whitehouse, and Jonathan Grigg; Genomics and Child Health, Blizard Institute, Queen Mary University of London, London, United Kingdom. RATIONALE: Vulnerability to pneumococcal infection is increased by exposure to particulate matter (PM) air pollution. Bacterial adherence to host cells is key to infection. A mechanism by which pneumococci adhere to airway cells is by co-opting the platelet activating factor receptor (PAFR). We previously reported that in vitro PAFR expression is increased by PM (1). In this study, we sought evidence that nasal PAFR expression is associated with urban PM exposure in vivo. METHODS: Nasal biopsies from healthy volunteers were taken 1 h before and 1h after moving though high pollution areas in London. Exposure was validated by personal black carbon (BC) monitoring (ng/m3). Nasal epithelial PAFR expression was assessed by PAFR monoclonal antibody and flow cytometry. Data are expressed as median fluorescence intensity (MFI) adjusting for isotypic control. The study was approved by a local research ethics committee. Data were analysed by paired t test, and Pearson correlation. RESULTS: Three paired nasal biopsies were obtained from two individuals. Personal BC was increased during exposure to a high pollution area (mean BC ng/m3: 369 vs 10298 p
