title: Ling Zhi-8: a novel T cell mitogen induces cytokine production and upregulation of ICAM-1 expression.
abstract: Ling Zhi-8 (LZ-8) is a protein purified from Ganoderma lucidium, a Chinese medicinal fungus thought to possess potent effects on the immune system. When examined for its effects on lymphocytes, LZ-8 exhibited potent mitogenic effects on human peripheral blood lymphocytes (PBL), inducing a bell-shaped dose-response curve similar to that caused by PHA and other lectin mitogens. Fractionation experiments indicated that the proliferative response in the PBL cultures was primarily due to T cells, but was monocyte dependent. Stimulation of PBL with LZ-8 resulted in the production of IL-2 and a corresponding upregulation of IL-2 receptor expression. In addition to T cell proliferation, microscopic examination of LZ-8-stimulated PBL revealed that LZ-8 induced cellular aggregate formation. The aggregate formation correlated with a dramatic rise in ICAM-1 expression and an increased production of IFN-gamma, TNF alpha, and IL-1 beta, molecules associated with regulation of ICAM-1 expression. Both the aggregate formation and the proliferative effects of LZ-8 were blocked by addition of monoclonal antibody to either CD18 or CD11a, the counterreceptor complex components for ICAM-1. Furthermore, addition of neutralizing antibodies to both IL-2 receptor and TNF alpha blocked aggregate formation, cellular proliferation, and ICAM-1 expression. These findings demonstrate that LZ-8 is a potent T cell activator, mediating its effects via cytokine regulation of integrin expression.
authors.affiliation: Immunology Department, Genentech, Inc., South San Francisco, California 94080.
authors.forename: M
authors.initials: M
authors.lastname: Haak-Frendscho
authors.forename: K
authors.initials: K
authors.lastname: Kino
authors.forename: T
authors.initials: T
authors.lastname: Sone
authors.forename: P
authors.initials: P
authors.lastname: Jardieu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002449:Cell Aggregation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D005656:Fungal Proteins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008934:Mitogens / Q000302:isolation & purification*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D005656:Fungal Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D008934:Mitogens; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1