Yutaka Ueda1,2,3, Kazuyuki Nakagome4,5, Takehito Kobayashi1,3, Toru Noguchi1,3, Tomoyuki Soma1,3, Katsuyo Ohashi-Doi6, Kenichi Tokuyama2,3, Makoto Nagata1,3. 1. Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan. 2. Department of Pediatrics, Saitama Medical University, Saitama, Japan. 3. Allergy Center, Saitama Medical University, Saitama, Japan. 4. Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan, nakagomek-tky@umin.ac.jp. 5. Allergy Center, Saitama Medical University, Saitama, Japan, nakagomek-tky@umin.ac.jp. 6. Torii Pharmaceutical Co. Ltd., Tokyo, Japan.
Abstract
BACKGROUND: Even in subjects who are not sensitized to house dust mite (HDM), allergic symptoms can be aggravated by exposure to dust, suggesting that innate immune responses may be involved in these processes. Since eosinophils express pattern recognition receptors, HDM may directly upregulate eosinophil functions through these re ceptors. The objective of this study was to examine whether Dermatophagoides farinae (Df), a representative HDM, or Der f 1, a major allergen of Df, modifies the effector functions of eosinophils. METHODS: Eosinophils isolated from the blood of healthy donors or allergic patients were stimulated with Df extract or Der f 1, and their adhesion to recombinant human intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of the eosinophil superoxide anion (O2-) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by ELISA as a marker of degranulation. RESULTS: Df extract or Der f 1 directly induced eosinophil adhesion to ICAM-1, O2- generation, and EDN release. Anti-αM- or anti-β2-integrin antibodies or protease-activated receptor (PAR)-2 antagonists suppressed the eosinophil adhesion, O2- generation, and EDN release induced by Df extract or Der f 1. Eosinophils from allergic patients showed higher adhesion to ICAM-1 than those from healthy donors. CONCLUSIONS: These findings suggested that Df extract and Der f 1 directly activate eosinophil functions through αMβ2-integrin and PAR-2. Eosinophil activation by HDM may play roles in the aggravation of allergic symptoms, not only in HDM-sensitized patients, but also in nonsensitized patients.
BACKGROUND: Even in subjects who are not sensitized to house dust mite (HDM), allergic symptoms can be aggravated by exposure to dust, suggesting that innate immune responses may be involved in these processes. Since eosinophils express pattern recognition receptors, HDM may directly upregulate eosinophil functions through these re ceptors. The objective of this study was to examine whether Dermatophagoides farinae (Df), a representative HDM, or Der f 1, a major allergen of Df, modifies the effector functions of eosinophils. METHODS: Eosinophils isolated from the blood of healthy donors or allergicpatients were stimulated with Df extract or Der f 1, and their adhesion to recombinant humanintercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of the eosinophil superoxide anion (O2-) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by ELISA as a marker of degranulation. RESULTS:Df extract or Der f 1 directly induced eosinophil adhesion to ICAM-1, O2- generation, and EDN release. Anti-αM- or anti-β2-integrin antibodies or protease-activated receptor (PAR)-2 antagonists suppressed the eosinophil adhesion, O2- generation, and EDN release induced by Df extract or Der f 1. Eosinophils from allergicpatients showed higher adhesion to ICAM-1 than those from healthy donors. CONCLUSIONS: These findings suggested that Df extract and Der f 1 directly activate eosinophil functions through αMβ2-integrin and PAR-2. Eosinophil activation by HDM may play roles in the aggravation of allergic symptoms, not only in HDM-sensitized patients, but also in nonsensitized patients.