title: The effect of hepatocyte growth factor on secretory functions in human eosinophils.
abstract: Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study. We found that HGF significantly inhibited IL-5-induced secretion of TGF-β and VEGF from human eosinophils. The inhibitory effect is not associated with TGF-β transcription; rather, it is associated with ultrastructural granule emptying and loss of intracellular TGF-β contents, indicating HGF inhibits the process of piecemeal degranulation. The effect of HGF on extracellular trap cell death (ETosis) that mediates cytolytic degranulation was also investigated; however, immobilized IgG- or phorbol myristate acetate-induced ETosis was only minimally attenuated by HGF. These results reveal the effect of HGF on the distinct pathways of eosinophil secretory functions and also provide novel insights into the role of HGF in the pathogenesis of allergic inflammation.
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamauchi
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. Electronic address: ueki-shige@nifty.com.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Ueki
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Konno
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan; Nagareyama Tobu Clinic, 909-1 Nazukari, Nagareyama City, Chiba 270-0145, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ito
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Nishikawa
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moritoki
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Omokawa
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Saga
authors.affiliation: Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hirokawa
mesh_terms: D004804:Eosinophils / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C066855:HGF protein, human; C508599:IL5 protein, human; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor
keywords: Asthma; ETosis; Eosinophils; HGF; TGF-β; VEGF