title: Essential role of monocytes in the in vitro production of IL-4 and nonspecific IgE antibody by peripheral blood lymphocytes from mice sensitized s.c. once with cedar pollen.
abstract: To explore which cytokine or cell is essential for the production of antibodies (Abs) of the IgE class in allergic diseases, we injected cedar pollen into wild-type, interferon-gamma(-/-) (IFN-gamma(/)), or interleukin-4(-/-) (IL-4(-/-)) BALB/c mice through four (i.n., i.p., s.c., and i.v.) different routes without adjuvant. Wild-type or IFN-gamma(-/-), but not IL-4(-/-), mice sensitized once or twice showed a significant increase in total IgE Ab in their serum, revealing the essential role of IL-4 in the production of total IgE Ab. We separated peripheral blood mononuclear cells (PBMCs) from untreated or sensitized mice into monocyte-rich, lymphocyte-rich, and granulocyterich populations by Percoll density-gradient centrifugation or into specific antigen cells by flow cytometry, cultured the cells in various combinations, and examined the levels of cytokines and IgE Ab released into the medium. The PBMCs from mice sensitized s.c. once, but not those from untreated animals, produced significant amounts of IL-4 and total IgE Ab, whereas the lymphocyte-rich population alone did not. Unexpectedly, IL-4 and IgE Ab production was restored by the addition of Mac-1(+) cells in the monocyte-rich fraction to the lymphocyte-rich fraction. These results indicate the essential role of monocytes in the production of IL-4 and total IgE Ab by lymphocytes during the initial stage of sensitization.
authors.affiliation: Department of Physiology, Osaka Medical College, Takatsuki 569-8686, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Junko
authors.initials: J
authors.lastname: Tashiro-Yamaji
authors.forename: Kanji
authors.initials: K
authors.lastname: Sakurai
authors.forename: Masako
authors.initials: M
authors.lastname: Miyoshi-Higashino
authors.forename: Hayahito
authors.initials: H
authors.lastname: Nomi
authors.forename: Sayako
authors.initials: S
authors.lastname: Miura-Takeda
authors.forename: Masashi
authors.initials: M
authors.lastname: Okada
authors.forename: Satoko
authors.initials: S
authors.lastname: Yamaguchi
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; D028203:Cedrus; D018929:Cell Culture Techniques; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011058:Pollen / Q000276:immunology*
chemical_list: D000485:Allergens; D016177:Macrophage-1 Antigen; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma