title: Thrombomodulin inhibits the activation of eosinophils and mast cells.
abstract: Eosinophils and mast cells play critical roles in the pathogenesis of bronchial asthma. Activation of both cells leads to the release of pro-inflammatory mediators in the airway of asthmatic patients. Recently, we have shown that inhaled thrombomodulin inhibits allergic bronchial asthma in a mouse model. In the present study, we hypothesize that thrombomodulin can inhibit the activation of eosinophils and mast cells. The effect of thrombomodulin on the activation and release of inflammatory mediators from eosinophils and mast cells was evaluated. Thrombomodulin inhibited the eotaxin-induced chemotaxis, upregulation of CD11b and degranulation of eosinophils. Treatment with thrombomodulin also significantly suppressed the degranulation and synthesis of inflammatory cytokines and chemokines in eosinophils and mast cells. Mice treated with a low-dose of inhaled thrombomodulin have decreased number of eosinophils and activated mast cells and Th2 cytokines in the lungs compared to untreated mice. The results of this study suggest that thrombomodulin may modulate allergic responses by inhibiting the activation of both eosinophils and mast cells.
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan.
authors.forename: Ziaurahman
authors.initials: Z
authors.lastname: Roeen
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan.
authors.forename: Corina N
authors.initials: CN
authors.lastname: D'Alessandro-Gabazza
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Onishi
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Yasuma
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan; Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Urawa
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Taguchi
authors.affiliation: Department of Immunology, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514-8507, Japan. Electronic address: gabazza@doc.medic.mie-u.ac.jp.
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Gabazza
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D015550:Cell Degranulation; D045744:Cell Line, Tumor; D054413:Chemokine CCL11 / Q000187:drug effects / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D010047:Ovalbumin; D061251:Primary Cell Culture; D011994:Recombinant Proteins / Q000008:administration & dosage; D058408:Th1-Th2 Balance; D018180:Thrombomodulin / Q000008:administration & dosage*
chemical_list: D039481:CD11b Antigen; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D016207:Cytokines; D011994:Recombinant Proteins; C546931:THBD protein, human; D018180:Thrombomodulin; D010047:Ovalbumin
keywords: Asthma; Coagulation; Eosinophils; Mast cells; Protein C pathway