title: Essential role of macrophages in the initiation of allergic rhinitis in mice sensitized intranasally once with cedar pollen: regulation of class switching of immunoglobulin in B cells by controlling interleukin-4 production in T cells of submandibular lymph nodes.
abstract: The production of allergen-specific IgE antibodies (Abs) in allergen-sensitized patients or animals has a mutual relationship with the immunologic response leading to allergic rhinitis. We recently reported that, after an intranasal injection of cedar pollen into mice, an interleukin-4 (IL-4)-dependent increase in serum nonspecific IgE Abs was a prerequisite for the production of serum allergen-specific IgE Abs. Here, we explored which lymphoid organs were responsive to the intranasally injected allergen and how IL-4 and IgE Abs were produced in the lymphocytes. Time-dependent changes in the total cell numbers and in in vitro IgE Ab production in various lymphoid organs revealed that the submandibular lymph nodes were the main responsible organ. After treatment with allergen (for IgE production) or allergen and complete Freund's adjuvant (for IgG production), we separated submandibular lymph node cells into macrophage-, lymphocyte-, and granulocyte-rich populations by discontinuous Percoll density-gradient centrifugation. Unexpectedly, bulk cells, but not the lymphocyte- or macrophage-rich populations, produced significant amounts of IL-4, IgE, and IgG; whereas production was restored by addition of Mac-1(+)  cells from the macrophage-rich to the lymphocyte-rich fraction. Furthermore, a combination of the lymphocyte-rich population (for IgG [or IgE]) production) and the macrophage-rich population (for IgE [or IgG]) production) produced a large amount of IgE (or IgG). These results indicate that, in the initiation of allergic rhinitis, macrophages in the submandibular lymph nodes are essential not only for IL-4 or immunoglobulin production, but also for class switching of immunoglobulin in lymphocytes.
authors.affiliation: Department of Physiology, Osaka Medical College, Takatsuki 569-8686, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Hirano
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ogita-Nakanishi
authors.forename: Wakako
authors.initials: W
authors.lastname: Miyachi
authors.forename: Natsuki
authors.initials: N
authors.lastname: Hannya
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamamoto-Kimoto
authors.forename: Kanji
authors.initials: K
authors.lastname: Sakurai
authors.forename: Masako
authors.initials: M
authors.lastname: Miyoshi-Higashino
authors.forename: Junko
authors.initials: J
authors.lastname: Tashiro-Yamaji
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ijiri
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kanazawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Terada
authors.forename: Ryo
authors.initials: R
authors.lastname: Kawata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takenaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kubota
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Yoshida
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D028203:Cedrus / Q000737:chemistry; D007114:Immunization; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D007136:Immunoglobulins; D015847:Interleukin-4; D007073:Immunoglobulin E