Abstract
Ganoderma lucidum, also known as LINGZHI, has a long tradition of use in folk medicine of the Far East, which is documented in the oldest Chinese pharmacopoeia, declaring it a superior medicine. LINGZHI-8 (LZ-8) is an immunoregulatory fungal protein isolated from the fruiting body of Ganoderma lucidum. Neutropenia is a condition with an abnormally low levels of neutrophils in the blood, which is caused by numerous medical conditions or medications, such as chemotherapy. The current study demonstrated that recombinant LZ-8 (rLZ-8) from Pichia promoted the differentiation of bone marrow hematopoietic stem cells (HSCs) into granulocytes in a neutropenia mouse model induced by cyclophosphamide. Also, it regulated the CXCR4-SDF1 axis to promote the mobilization of HSCs and the release of neutrophils from the bone marrow to peripheral blood. Binding of rLZ-8 to the colony stimulating factor 1 receptor (CSF1R) promotes the differentiation of HSCs into primitive CFU colonies. These results suggested that rLZ-8 has a potential effect in the treatment of chemotherapy-induced neutropenia.
Highlights
Ganoderma lucidum is a major medicinal fungus widely used in traditional Chinese medicine
A large amount of recombinant LZ-8 (rLZ-8) was accumulated in the medium with mass similar to that of the native LZ-8 protein and slightly larger than the theoretical molecular weight calculated based on the amino acid sequences
In order to confirm that the main component of leukocytes in peripheral blood was neutrophils under the action of rLZ-8, we evaluated the changes in the number of neutrophils during treatment in the mice from the normal, model, Granulocyte colony-stimulating factor (G-CSF), and rLZ-8 groups by flow cytometry (Figure 3A)
Summary
Ganoderma lucidum is a major medicinal fungus widely used in traditional Chinese medicine. LZ-8 induced the activation and maturation of human dendritic cells via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and mitogen-activated protein kinase (MAPK) pathways (Lin et al, 2009) It served as a potential adjuvant for the development of DNA vaccines for human cancers owing to its stimulatory activity on dendritic cells (Chu et al, 2011).
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