title: RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge.
abstract: RANTES (CC chemokine ligand 5) contributes to airway inflammation through accumulation of eosinophils, but the exact role of RANTES (CCL5) is not defined. C57BL/6 mice, sensitized by injection of ovalbumin (OVA) on Days 1 and 14, were challenged with OVA on Days 28, 29, and 30 (3 challenges, short-term-challenge model) or on Days 28, 29, 30, 36, 40, 44, and 48 (7 challenges, repeated-challenge model) and evaluated 48 h later. Anti-mouse RANTES was given intravenously, and recombinant mouse RANTES or PBS was given intratracheally. These reagents were given on Days 28, 29, and 30 in the short-term-challenge study and on Days 44 and 48 in the repeated-challenge study. After short-term challenge, there were no effects after administration of anti-RANTES or RANTES. In the repeated-challenge study, although control mice showed a decrease in airway hyperresponsiveness, administration of anti-RANTES sustained and enhanced airway hyperresponsiveness and increased goblet cell numbers. In contrast, administration of RANTES normalized airway function but reduced goblet cell numbers. IL-12 and IFN-gamma levels in BAL decreased in the anti-RANTES group and increased in the RANTES group. IFN-gamma-producing CD4 T cells in lung, and IFN-gamma production from lung T cells in response to OVA in the anti-RANTES group, were significantly decreased but were increased in the RANTES group. Anti-IFN-gamma, administered with RANTES, decreased the effects of RANTES on AHR after repeated challenge. These data indicate that RANTES plays a role in the regulation of airway function after repeated allergen challenge, in part through modulation of levels of IFN-gamma and IL-12.
authors.affiliation: Department of Pediatrics, Division of Cell Biology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Koya
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Taku
authors.initials: T
authors.lastname: Kodama
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miyahara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsubara
authors.forename: Annette
authors.initials: A
authors.lastname: Balhorn
authors.forename: Anthony
authors.initials: A
authors.lastname: Joetham
authors.forename: Azzedine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018946:Chemokine CCL5 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005260:Female; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D018664:Interleukin-12 / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology*
chemical_list: D000485:Allergens; D018946:Chemokine CCL5; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin