Abstract
Alkylglycerols (AKGs) are ether-linked glycerols derived from shark liver oil and found in small amounts in human milk. Previous studies showed that oral AKGs administration significantly increased the immune response in mice. The aim of the present study was to investigate the in vitro immunomodulatory effect of AKGs on stimulating splenic lymphocyte responses. C57BL/6 mice were immunized with hepatitis B surface antigen (HBsAg). Splenic B cells were purified and stimulated with anti-BCR and anti-CD38. Meanwhile, splenic CD4+ T cells were purified and stimulated with anti-CD3 and anti-CD28. For antigen specific stimulation, the purified CD4+ T cells were cocultured with HBsAg -pulsed dendritic cells. The stimulated lymphocytes were treated with different concentrations of AKGs. The cell proliferation was assessed by [3H]-thymidine incorporation assay. The maturation of B cells was assessed by examining the germline (GL) transcription of IgG (γ1) mRNA expression, and the surface expressions of CD80/CD86 markers were examined by flow cytometry analysis. Th1/Th2 polarity was assessed by T-BET (Th1)/GATA-3 (Th2) flow cytometry assay and by characteristic cytokines ELISA assay (TNF-α and IFN-γ for Th1; IL-4 and IL-10 for Th2). It was found that AKGs significantly increased the BCR/CD38 -stimulated B cell proliferation. The T cell proliferation in response to CD3/CD28 or specific antigen stimulation was also increased by AKGs. The transcriptional level of IgG (γ1) and the expressions of CD80/CD86 molecules were markedly increased by AKGs in BCR/CD38 -stimulated B cells. Meanwhile, the results showed that AKGs increased the expression of T-BET transcriptional factor and the production of Th1 cytokines (TNF-α and IFN-γ) upon CD3/CD28 stimulation; whereas, levels of Th2 cytokines (IL-4 and IL-10) were decreased by AKGs. Our study demonstrated that AKGs can modulate immune responses by boosting the proliferation and maturation of murine lymphocytes in vitro.
Highlights
Shark liver oil (SLO) is purified from sharks that live in cold, deep oceans
The enhancement of macrophage ingestion activity by AKGs treatment depends on the signaling crosstalk between macrophage and nonadherent cells (T and B cells), which indicates that the physiological roles of AKGs in immune system are contributed by the coordination of various immune cells
Since high yield of specific antibody in response to vaccination was known to be dependent on primed T cells, we studied the impact of AKGs on the proliferation and activation of splenic T cells stimulated through CD3/CD28 or antigen-pulsed dendritic cells (DCs)
Summary
Shark liver oil (SLO) is purified from sharks that live in cold, deep oceans. It contains alkylglycerols (AKGs), squalene, pristane, lipid-soluble vitamins (A and D), V-3 fatty acids, triglycerides and other unsaturated fatty acids [1]. AKGs are considered to be important immune stimulating factors, and are able to increase the number of leucocytes, lymphocytes and platelets. They can be applied to treat leukemia, and even solid tumor [3]. It was demonstrated that human milk can enhance antibody response after vaccination [6]. The enhancement of macrophage ingestion activity by AKGs treatment depends on the signaling crosstalk between macrophage and nonadherent cells (T and B cells), which indicates that the physiological roles of AKGs in immune system are contributed by the coordination of various immune cells
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