Potentiation of T cell function by a marine algae-derived sulfated polymannuroguluronate: in vitro analysis of novel mechanisms.
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.
Xia
Wei
W
Department of Pharmacology, Marine Drug and Food Institute, Ocean University of China.
Li
Jing
J
Geng
Meiyu
M
Xin
Xianliang
X
Ding
Jian
J
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects / Q000235:genetics; D016516:CD4-CD8 Ratio / Q000706:statistics & numerical data; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000639:trends; D056890:Eukaryota / Q000737:chemistry / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000099192:CD69 Antigens
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003208:Concanavalin A; D016207:Cytokines; D007376:Interleukin-2; D037181:Lectins, C-Type; D011134:Polysaccharides; D000099192:CD69 Antigens; C489185:sulfated polymannuroguluronate