title: Helicobacter pylori outer membrane vesicle proteins induce human eosinophil degranulation via a β2 Integrin CD11/CD18- and ICAM-1-dependent mechanism.
abstract: Eosinophil cationic protein (ECP), a cytotoxic protein contained in eosinophils granules, can contribute to various inflammatory responses. Although Helicobacter pylori infection increases infiltration of eosinophils, the mechanisms of eosinophil degranulation by H. pylori infection are largely unknown. The goal of this study was to investigate the role of H. pylori outer membrane vesicles (OMVs) in modulating eosinophil degranulation. We found that eosinophils treated with H. pylori OMVs released significantly more ECP compared with untreated controls. In addition, eosinophils cocultured with OMV-preexposed primary gastric epithelial cells exhibited significantly increased ECP release. Similarly, eosinophils cocultured with culture supernatant (CM) from primary gastric epithelial cells exposed to OMVs (OMV-CM) released significantly higher amounts of ECP compared with eosinophils cocultured with CM from unexposed control cells. Furthermore, OMVs and OMV-CM both induced the upregulation of ICAM-1 on gastric epithelial cells and β2 integrin CD11b on eosinophils. In addition, both transduction of ICAM-1 shRNA into gastric epithelial cells and treatment with neutralizing mAbs to CD18 significantly decreased OMV-mediated or OMV-CM-mediated release of ECP. These results suggest that the eosinophil degranulation response to H. pylori OMVs occurs via a mechanism that is dependent on both β2 integrin CD11/CD18 and ICAM-1.
authors.affiliation: Department of Microbiology and Department of Biomedical Science, Hanyang University College of Medicine and Graduate School of Biomedical Science and Engineering, Sungdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Su Hyuk
authors.initials: SH
authors.lastname: Ko
authors.affiliation: Department of Microbiology and Department of Biomedical Science, Hanyang University College of Medicine and Graduate School of Biomedical Science and Engineering, Sungdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Jong Ik
authors.initials: JI
authors.lastname: Jeon
authors.affiliation: Department of Biotechnology, Joongbu University, Choongnam, Republic of Korea.
authors.forename: Young-Jeon
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ho Joo
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Republic of Korea.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea ; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Department of Biomedical Science, Hanyang University College of Medicine and Graduate School of Biomedical Science and Engineering, Sungdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D039481:CD11b Antigen / Q000032:analysis; D018821:CD18 Antigens / Q000502:physiology*; D015550:Cell Degranulation; D047150:Eosinophil Cationic Protein / Q000502:physiology; D004804:Eosinophils / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000209:etiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D039481:CD11b Antigen; D018821:CD18 Antigens; C509295:ITGAM protein, human; D018799:Intercellular Adhesion Molecule-1; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human
references.citation: J Med Microbiol. 2008 Feb;57(Pt 2):145-50
references.pmid: 18201978
references.citation: J Immunol. 1998 May 15;160(10):4889-95
references.pmid: 9590236
references.citation: PLoS One. 2013;8(5):e64216
references.pmid: 23717571
references.citation: Cell Microbiol. 2009 Mar;11(3):488-505
references.pmid: 19046339
references.citation: Front Pharmacol. 2013 Apr 01;4:33
references.pmid: 23554594
references.citation: Immunology. 2012 Sep;137(1):98-113
references.pmid: 22862554
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1171-80
references.pmid: 12919943
references.citation: Microbes Infect. 2012 Jan;14(1):9-16
references.pmid: 21911076
references.citation: Eur J Immunol. 2010 Jun;40(6):1651-62
references.pmid: 20333629
references.citation: FEMS Microbiol Lett. 2000 Jan 15;182(2):259-64
references.pmid: 10620676
references.citation: Hum Pathol. 2008 Sep;39(9):1360-9
references.pmid: 18614201
references.citation: Mediators Inflamm. 2004 Dec;13(5-6):369-72
references.pmid: 15770055
references.citation: J Pathol. 1999 Jun;188(2):220-6
references.pmid: 10398168
references.citation: Mod Pathol. 1993 May;6(3):281-9
references.pmid: 8346176
references.citation: J Bacteriol. 1992 Feb;174(4):1370-7
references.pmid: 1735724
references.citation: J Biol Chem. 2011 Jul 15;286(28):25256-64
references.pmid: 21596743
references.citation: Infect Immun. 2005 Nov;73(11):7602-12
references.pmid: 16239564
references.citation: J Immunol. 1994 Jun 1;152(11):5457-67
references.pmid: 7514638
references.citation: Infect Immun. 2007 Jul;75(7):3373-81
references.pmid: 17452475
references.citation: Infect Immun. 2010 Dec;78(12):5054-61
references.pmid: 20876296
references.citation: J Clin Gastroenterol. 1997;25 Suppl 1:S215-21
references.pmid: 9479651
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10939-44
references.pmid: 8855287
references.citation: Gut. 2009 May;58(5):721-32
references.pmid: 19052023
references.citation: J Mol Med (Berl). 2014 Apr;92(4):411-27
references.pmid: 24362517
references.citation: Front Immunol. 2014 Oct 27;5:496
references.pmid: 25386174
references.citation: Adv Immunol. 2009;101:81-121
references.pmid: 19231593
references.citation: J Pathol. 1999 May;188(1):24-9
references.pmid: 10398136
references.citation: Clin Exp Immunol. 2011 Oct;166(1):34-45
references.pmid: 21910723
references.citation: Am J Pathol. 2011 Apr;178(4):1448-52
references.pmid: 21406172
references.citation: Dig Dis Sci. 1991 Apr;36(4):435-40
references.pmid: 2007361
references.citation: J Mol Med (Berl). 2009 Feb;87(2):169-80
references.pmid: 18985311
references.citation: Gut. 2005 Dec;54(12):1822
references.pmid: 16284301
references.citation: J Leukoc Biol. 2008 Jan;83(1):1-12
references.pmid: 17906117
references.citation: J Immunol. 2011 Aug 15;187(4):1931-41
references.pmid: 21724992
references.citation: Curr Drug Targets Inflamm Allergy. 2005 Jun;4(3):305-11
references.pmid: 16101538
references.citation: J Gastroenterol Hepatol. 2015 Jan;30(1):99-108
references.pmid: 25041690
references.citation: Int J Immunopathol Pharmacol. 2013 Jul-Sep;26(3):647-62
references.pmid: 24067461