beta-escin and Asthma

Molecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils.. An ovalbumin (OVA)-based model was used to induce asthma-like experimental allergic airway disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h-72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs.. We show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time.

Topics: Animals; Antigens, Differentiation, Myelomonocytic; Asthma; Dexamethasone; Disease Models, Animal; Eosinophilia; Escin; Female; Gene Expression Regulation; Macrophages; Mice; Mice, Inbred BALB C; Optical Imaging; Sialic Acid Binding Immunoglobulin-like Lectins; Treatment Outcome

Type I hypersensitivity is characterized by the overreaction of the immune system against otherwise innocuous substances. It manifests as allergic rhinitis, allergic conjunctivitis, allergic asthma or atopic dermatitis if mast cells are activated in the respective organs. In case of systemic mast cell activation, life-threatening anaphylaxis may occur. Currently, type I hypersensitivities are treated either with glucocorticoids, anti-histamines, or mast cell stabilizers. Although these drugs exert a strong anti-allergic effect, their long-term use may be problematic due to their side-effects.. In the course of a routine in vitro screening process, we identified beta-escin as a potentially anti-allergic compound. Here we tested beta-escin in two mouse models to confirm this anti-allergic effect in vivo. In a model of the early phase of allergic reactions, the murine passive cutaneous anaphylaxis model, beta-escin inhibited the effects of mast cell activation and degranulation in the skin and dose-dependently prevented the extravasation of fluids into the tissue. Beta-escin also significantly inhibited the late response after antigen challenge in a lung allergy model with ovalbumin-sensitized mice. Allergic airway inflammation was suppressed, which was exemplified by the reduction of leucocytes, eosinophils, IL-5 and IL-13 in the bronchoalveolar lavage fluid. Histopathological examinations further confirmed the reduced inflammation of the lung tissue. In both models, the inhibitory effect of beta-escin was comparable to the benchmark dexamethasone.. We demonstrated in two independent murine models of type I hypersensitivity that beta-escin has potent anti-allergic properties. These results and the excellent safety profile of beta-escin suggest a therapeutic potential of this compound for a novel treatment of allergic diseases.

Topics: Animals; Anti-Allergic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cell Movement; Cytokines; Dose-Response Relationship, Drug; Eosinophils; Escin; Hypersensitivity; Lung; Mice; Models, Animal; Ovalbumin; Passive Cutaneous Anaphylaxis; Pneumonia; Time Factors; Treatment Outcome

More than 400 agents are recognized as causes of occupational asthma, a work-related disease that can be induced by an immunologic or a nonimmunologic mechanism.. To describe a 57-year-old man employed in the pharmaceutical industry who developed bronchial asthma while working with products such as Plantago ovata and aescin, an active ingredient with anti-inflammatory and venotonic properties.. Various tests were performed, including radiography, total serum IgE titer measurements, skin tests against common pneumoallergens and Plantago species, pulmonary function studies, a methacholine test, and specific inhalation challenge with P. ovata and aescin.. The results of these tests, including specific inhalation challenge, confirmed the diagnosis of occupational asthma due to aescin exposure, whereas the results of specific challenge with P. ovata, a known cause of occupational asthma, were negative.. Aescin may represent a new causative agent of occupational asthma in personnel working in the pharmaceutical industry. The mechanism by which aescin can produce asthma is unknown, but analysis of the characteristics of our patient suggests a non-IgE immunologic mechanism, although an irritative mechanism secondary to long-term low-level exposure to aescin, a possible irritant, cannot be ruled out.

Topics: Asthma; Escin; Humans; Inhalation; Male; Middle Aged; Occupational Diseases; Occupational Exposure; Psyllium; Skin Tests