title: The Effects of Antigen-Specific IgG1 Antibody for the Pulmonary-Hypertension-Phenotype and B Cells for Inflammation in Mice Exposed to Antigen and Fine Particles from Air Pollution.
abstract: Air pollution is known to exacerbate chronic inflammatory conditions of the lungs including pulmonary hypertension, cardiovascular diseases and autoimmune diseases. Directly pathogenic antibodies bind pro-inflammatory cell receptors and cause or exacerbate inflammation. In contrast, anti-inflammatory antibody isotypes (e.g. mouse immunoglobulin G1, IgG1) bind inhibitory cell receptors and can inhibit inflammation. Our previous studies showed that co-exposure to antigen and urban ambient particulate matter (PM2.5) induced severe pulmonary arterial thickening and increased right ventricular systolic pressures in mice via T-cell produced cytokines, Interleukin (IL)-13 and IL-17A. The aim of the current study was to understand how B cell and antibody responses integrate into this T cell cytokine network for the pulmonary hypertension phenotype. Special focus was on antigen-specific IgG1 that is the predominant antibody in the experimental response to antigen and urban ambient PM2.5. Wild type and B cell-deficient mice were primed with antigen and then challenged with antigen and urban particulate matter and injected with antibodies as appropriate. Our data surprisingly showed that B cells were necessary for the development of increased right ventricular pressures and molecular changes in the right heart in response to sensitization and intranasal challenge with antigen and PM2.5. Further, our studies showed that both, the increase in right ventricular systolic pressure and right ventricular molecular changes were restored by reconstituting the B cell KO mice with antigen specific IgG1. In addition, our studies identified a critical, non-redundant role of B cells for the IL-17A-directed inflammation in response to exposure with antigen and PM2.5, which was not corrected with antigen-specific IgG1. In contrast, IL-13-directed inflammatory markers, as well as severe pulmonary arterial remodeling induced by challenge with antigen and PM2.5 were similar in B cell-deficient and wild type mice. Our studies have identified B cells and antigen specific IgG1 as potential therapeutic targets for pulmonary hypertension associated with immune dysfunction and environmental exposures.
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York, United States of America.
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York, United States of America.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York, United States of America.
authors.forename: Nedim
authors.initials: N
authors.lastname: Durmus
authors.affiliation: Department of Medicine, Division of Pulmonary Medicine, New York University Langone Medical Center, New York, New York, United States of America.
authors.forename: Bertram
authors.initials: B
authors.lastname: Bleck
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York, United States of America; Department of Medicine, Division of Pulmonary Medicine, New York University Langone Medical Center, New York, New York, United States of America.
authors.forename: Joan
authors.initials: J
authors.lastname: Reibman
authors.affiliation: Clinic for Rheumatology, University of Lübeck, Lübeck, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, New York, United States of America; Department of Medicine, Division of Pulmonary Medicine, New York University Langone Medical Center, New York, New York, United States of America.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Grunig
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects; D000818:Animals; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D001794:Blood Pressure / Q000187:drug effects / Q000276:immunology; D006976:Hypertension, Pulmonary / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D052638:Particulate Matter / Q000009:adverse effects*; D010641:Phenotype; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology
chemical_list: D000393:Air Pollutants; D000941:Antigens; D007074:Immunoglobulin G; D052638:Particulate Matter