Recombinant Ganoderma Immunomodulatory Protein Treated Mice Neutropenia Via Mobilizing Hematopoietic Stem Cells

As the most abundant white blood cells in the peripheral circulation-neutrophils play a fundamental role in the innate immune response, in the first line of the body against microbial pathogens. Due to the broad participation in various types of neutrophil tissue injury and its strong organization toxic effects, the generation of neutrophils in vivo is a tightly regulated process.Neutropenia syndrome refers to the number of neutrophils in the blood at a low concentration abnormality, the lower the neutrophil count means that the greater the risk of infection, all patients receiving chemotherapy treatment are faced with the development of neutropenia disease.Clinical use of colony-stimulating-factor stimulated neutrophil functional maturation and production, for the prevention and treatment of neutropenia disease. Blood cells are produced by the bone marrow hematopoiesis system, relying on a unique ability of self-renewal hematopoietic stem cells which can differentiate into all the features of pluripotent stem cells. Granulocyte colony stimulating factor can stimulate hematopoietic cells by mobilizing a large number of stem/progenitor cells into peripheral circulation. G-CSF induced chemokine stromal cell derived factor-1 (SDF-1) decreasing, and increased the expression of its receptor CXCR4 in the bone marrow (BM). SDF-1 decline and CXCR4 upregulation will cause the release of neutrophils from the bone marrow into the peripheral blood.Ganoderma immunomodulatory protein (LZ-8) as a protein having immunomodulatory function, showed anti-tumor effect, and in the treatment of thrombocytopenia in mice also showed a therapeutic effect, this study found that it can stimulate HSC proliferation in mice with cyclophosphamide-induced neutropenia disease, while promoting mature neutrophils releasing from the bone marrow into the peripheral blood by promoting the expression of CXCR4 and inhibiting SDF-1 secretion. rLZ-8 can promote HSC proliferation and promote myeloid progenitor cells to differentiate to achieve the neutral neutropenia treatment.