title: IgG immune complex induces the recruitment of inflammatory cells into the airway and TNF-mediated late airway hyperresponsiveness via NF-κB activation in mice.
abstract: BACKGROUND
  Many of the inflammatory proteins that are expressed in asthmatic airways are regulated, at least partially, by nuclear factor (NF)-κB. Blockade of NF-κB activity has resulted in attenuation of the cardinal features of asthma. Thus, delineating the mechanisms involved in NF-κB activation in asthma might provide an interesting approach to improving the management of asthma. However, despite its importance, the mechanism for NF-κB activation in asthma has not yet been determined.
  
  
  OBJECTIVE
  To examine the role of IgE and IgG antibodies (Abs) in the activation of NF-κB in mouse lungs.
  
  
  METHODS
  To examine the effect of IgE, mice underwent intratracheal (i.t.) instillation of an IgE immune complex (IgE-IC) (anti-2,4-dinitrophenyl hapten (DNP) IgE + DNP-BSA or DNP-OVA) and anaphylactogenic anti-IgE (LO-ME-2). For IgG, mice underwent i.t. instillation with a complex of anti-chicken gamma globulin (CGG) IgG1 mAb + CGG. NF-κB activation was determined by gel shift assay. Small interfering RNA was used for blockade of p50 expression. The effect of tumor necrosis factor (TNF) blockade was determined using anti-TNF Ab. A previously established murine model of asthma was used to assess airway hyperresponsiveness (AHR).
  
  
  RESULTS
  A single i.t. instillation of either IgE-IC or LO-ME-2 failed to induce activation of NF-κB in the lungs. In contrast, single i.t. instillation of IgG-IC was capable of inducing NF-κB activation, as well as NF-κB-dependent proinflammatory molecules, such as TNF and CXC chemokines. Pretreatment of p50 small interfering RNA decreased bronchoalveolar lavage fluid levels of TNF and macrophage inflammatory protein-2 induced by IgG-IC instillation. Single i.t. instillation of IgG-IC caused the recruitment of neutrophils and macrophages into the airway and TNF-mediated late AHR, but failed to induce Th2 cell-mediated asthmatic phenotypes.
  
  
  CONCLUSIONS
  IgG, but not IgE, is the major Ab that induces not only NF-κB activation and NF-κB-dependent proinflammatory molecules in the lungs but also subsequent recruitment of inflammatory cells into the airway and TNF-mediated late AHR.
authors.affiliation: Department of Immunology, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Lee
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Kim
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Kang
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Lee
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Ok-Hee
authors.initials: OH
authors.lastname: Chai
authors.forename: Chang-Ho
authors.initials: CH
authors.lastname: Song
authors.forename: Hae-Kyoung
authors.initials: HK
authors.lastname: Kim
authors.forename: Suhn-Young
authors.initials: SY
authors.lastname: Im
authors.forename: Dae-Kyu
authors.initials: DK
authors.lastname: Oh
authors.forename: Hern-Ku
authors.initials: HK
authors.lastname: Lee
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006632:Histamine / Q000276:immunology; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D048069:Tumor Necrosis Factors / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D034741:RNA, Small Interfering; D048069:Tumor Necrosis Factors; D007073:Immunoglobulin E; D006632:Histamine