Potentiation of T cell function by a marine algae-derived sulfated polymannuroguluronate: in vitro analysis of novel mechanisms.
نویسندگان
چکیده
Marine algae-derived sulfated polymannuroguluronate (SPMG), a candidate drug for AIDS treatment, was intraperitoneally injected into normal mice for 6 weeks, and the in vivo and in vitro mechanisms of SPMG for immunomodulation were investigated in isolated lymphocytes by MTT assay, flow cytometry, and surface plasmon resonance assay. SPMG treatment at 5 and 10 mg/kg enhanced concanavalin A (ConA)-induced T cell proliferation, cellular levels of CD69, interleukin-2 (IL-2), and interferon-gamma (IFN-gamma), as well as CD4/CD8 ratio, while decreasing tumor necrosis factor-alpha (TNF-alpha) level in T cells of peripheral blood mononuclear cells. In addition, 1 molecule of SPMG bound to 2/3 molecules of IL-2 with a K(D) of 9.53 x 10(-7) M. Heparin prevented SPMG binding to IL-2 by 72.2%; thus, to a large extent, SPMG and heparin share common binding sites on IL-2. In contrast, other glycosaminoglycans (e.g., chondroitin sulfate and dermatan sulfate) had little effect on SPMG and IL-2 interaction, suggesting the requirement of a defined sequence within the sugar chain for specific recognition of IL-2. Concomitant treatment of IL-2 and SPMG augmented lymphocyte proliferation, compared with IL-2 alone; in contrast, SPMG alone had no proliferative effect. Taken together, our findings demonstrated for the first time that SPMG exerted its immunomodulation by direct activation of T cell function, accompanied by simultaneous modulation of cytokine function, which suggests that SPMG would show great promise for use in anti-AIDS therapy.
منابع مشابه
Sulfated polymannuroguluronate (SPMG), a novel anti-acquired immune deficiency syndrome (AIDS) drug candidate, inhibits T cell apoptosis via combating oxidative damage of mitochondria
متن کامل
Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, inhibits T cell apoptosis by combating oxidative damage of mitochondria.
Sulfated polymannuroguluronate (SPMG) has entered the phase II clinical trial as the first anti-AIDS drug candidate in China. Herein, we report that SPMG was effective at protecting T lymphocytes against apoptosis. Further studies indicated that SPMG significantly elevated mitochondrial membrane potential (MMP) of T cells; inhibited mitochondrial release of cytochrome c (cyto c) in T cells; enh...
متن کاملOverview on Biological Activities and Molecular Characteristics of Sulfated Polysaccharides from Marine Green Algae in Recent Years
Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their nu...
متن کاملHypopigmenting Effects of Brown Algae-Derived Phytochemicals: A Review on Molecular Mechanisms
There is a rapid increase in the demand for natural hypopigmenting agents from marine sources for cosmeceutical and pharmaceutical applications. Currently, marine macroalgae are considered as a safe and effective source of diverse bioactive compounds. Many research groups are exploring marine macroalgae to discover and characterize novel compounds for cosmeceutical, nutraceutical, and pharmaceu...
متن کاملStructure, biology, evolution, and medical importance of sulfated fucans and galactans.
Sulfated fucans and galactans are strongly anionic polysaccharides found in marine organisms. Their structures vary among species, but their major features are conserved among phyla. Sulfated fucans are found in marine brown algae and echinoderms, whereas sulfated galactans occur in red and green algae, marine angiosperms, tunicates (ascidians), and sea urchins. Polysaccharides with 3-linked, b...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of pharmacological sciences
دوره 97 1 شماره
صفحات -
تاریخ انتشار 2005