A polysaccharide from Strongylocentrotus nudus eggs protects against myelosuppression and immunosuppression in cyclophosphamide-treated mice

• Published in: International immunopharmacology Vol. 11; no. 11; pp. 1946 - 1953
• Main Authors: Wang, Hui, Wang, Mengyu, Chen, Jing, Tang, Ying, Dou, Jie, Yu, Jian, Xi, Tao, Zhou, Changlin
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.11.2011; Elsevier
• Subjects: Animals; Biological and medical sciences; Bone Marrow - drug effects; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation - drug effects; Cells, Cultured; Cyclophosphamide - pharmacology; Dose-Response Relationship, Immunologic; Immune Tolerance - drug effects; Immunoglobulins - blood; Immunosuppression; Interleukin-2 - biosynthesis; Interleukin-2 - immunology; Macrophages - drug effects; Macrophages - immunology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Myelosuppression; Ovum - chemistry; Ovum - immunology; Phagocytosis - drug effects; Pharmacology. Drug treatments; PI3K/Akt; Polysaccharides - isolation & purification; Polysaccharides - pharmacology; SEP; Spleen - drug effects; Spleen - immunology; Spleen - pathology; Strongylocentrotus - immunology; Strongylocentrotus nudus; Thymus Gland - drug effects; Thymus Gland - immunology; Thymus Gland - pathology; Myelosuppression; Immunosuppression; SEP; PI3K/Akt; Antineoplastic agent; Echinodermata; Prevention; Echinoidea; Strongylocentrotus nudus; Egg; Enzyme; Transferases; Rodentia; Akt protein kinase; 1-Phosphatidylinositol 3-kinase; Alkylating agent; Oxazaphosphinane derivatives; Vertebrata; Cyclophosphamide; Mammalia; Treatment; Mouse; Nitrogen mustard; Animal; Invertebrata; Polysaccharide
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2011.06.006

To assess the chemoprotective properties of a polysaccharide from Strongylocentrotus nudus eggs (SEP), myelosuppressed and immunosuppressed mouse models were generated by administration of cyclophosphamide (Cy) and then treated with SEP. SEP (16mg/kg/d) remarkably increased spleen and thymus indices, activated the proliferation of leukocytes and erythrocytes and platelets from peripheral blood, and exhibited co-mitogenic activity on ConA- or LPS-stimulated splenocytes in a dose-dependent manner. An increased percentage of CD34+ cells in bone marrow of Cy-treated mice was also observed. Furthermore, SEP elevated CD4+ T lymphocyte counts as well as the CD4/CD8 ratio dose-dependently, and it increased interleukin-2 (IL-2), IgA, IgM, and IgG levels in the sera of Cy-treated mice. Pre-incubation with TLR2 and TLR4 blocking antibodies inhibited splenocyte proliferation and its IL-2 secretion. Finally, SEP significantly induced Akt phosphorylation in splenocytes from Cy-treated mice, suggesting that chemoprotection by SEP was mediated through the PI3K/Akt signaling pathway. These findings indicate that SEP plays an important role in the protection against myelosuppression and immunosuppression in Cy-treated mice and could be a potential immunomodulatory agent. ► We established immunosuppressed mouse models to evaluate the protective effects of SEP on cyclophosphamide-treated mice. ► Study demonstrated that SEP remarkably increased spleen and thymus indices, and splenocyte proliferation. ► SEP also enhanced haemopoietic function, T lymphocyte subsets as well as Ig levels in Cy-treated mice. ► Pre-incubation with TLR2 and TLR4 blocking antibodies inhibited splenocyte proliferation and IL-2 secretion induced by SEP. ► Furthermore, SEP could activate Akt phosphorylation which may play an important role in the chemoprotection of SEP.