title: Cell to cell contact through ICAM-1-LFA-1 and TNF-alpha synergistically contributes to GM-CSF and subsequent cytokine synthesis in DBA/2 mice induced by 1,3-beta-D-Glucan SCG.
abstract: SCG is a major 6-branched 1,3-beta-D-glucan in Sparassis crispa Fr. showing antitumor activity. We recently found that the splenocytes from naive DBA/1 and DBA/2 mice are potently induced by SCG to produce interferon- gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-12p70 (IL-12p70), and that GM-CSF plays a key biologic role among these cytokines. In this study, we investigated the contribution of cell-cell contact and soluble factors to cytokine induction by SCG in DBA/2 mice. Cell-cell contact involving intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) was an essential step for the induction of GM-CSF and IFN-gamma by SCG but not for the induction of TNF-alpha or IL-12p70 by SCG. SCG directly induced adherent splenocytes to produce TNF-alpha and IL-12p70. GM-CSF was required for the induction of TNF-alpha by SCG, and in turn, TNF-alpha enhanced the release of GM-CSF and thereby augmented the induction of IL-12p70 and IFN-gamma by SCG. Neutralization of IL-12 significantly inhibited the induction of IFN-gamma by SCG. We concluded that induction of GM-CSF production by SCG was mediated through ICAM-1 and LFA-1 interaction, GM-CSF subsequently contributed to further cytokine induction by SCG, and reciprocal actions of the cytokines were essential for enhancement of the overall response to SCG in DBA/2 mice.
authors.affiliation: Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy & Life Science, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Harada
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kawaminami
authors.forename: Noriko N
authors.initials: NN
authors.lastname: Miura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Adachi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakajima
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yadomae
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohno
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002450:Cell Communication; D016207:Cytokines / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor