Astragalus-polysaccharide Can Prompt The Release Of "High Quality" Mature Granulocytes From Bone Marrow Through Restoring L-selection Signaling Pathway After Chemotherapy

Background:Granulocytepenia after chemotherapy is a thorny problem in cancer therapy, and often leads to delay and termination of treatment. However, examination of smear of bone marrow shows active but not low hyperplasia in considerable amounts of patients with granulocytepenia. Therefore, we presume that the reason for granulocytepenia may be bone marrow polymorphonuclear leukocytes (BM-PMNL) cannot be released timely. Research shows that L-selectin expressed on BM-PMNL may participate in releasing of BM-PMNL from bone marrow to peripheral blood.Methods:In this study, rats were randomly divided into5groups:control group, cyclophosphamide group, CTX+APS group, CTX+G-CSF group and CTX+DXM group. Blood PMNL and mature BM granulocytes (band and segmented BM cells) were isolated using Percoll gradient centrifugation on d2, d4, d7, d10and d14after chemotherapy. Expression of L-selectin, PSGL-1, ADAM17and CD11b/CD18were assessed by flow cytometry, and chemotactic response to zymosan-activated serum (ZAS) was detected. We also counted band and segmented BM cells in smear of bone marrow and calculated percentage of PMNL in total blood white cells in peripheral blood smear.Results:APS, G-CSF and DXM can increase percentage of PMNL in peripheral blood and L-selectin expression on mature BM granulocytes after chemotherapy at different levels. Both APS and DXM group were significantly better than G-CSF group after7days post-chemotherapy (P<0.05). Compared with G-CSF and DXM, APS could significantly improve chemotactic ability of PMNL in mature BM granulocytes and peripheral blood after chemotherapy (P<0.05). Smear of bone marrow showed that percentage of band and segmented BM cells in myeloid cells increased gradually in APS, G-CSF and DXM group. The percentage at each time point were both higher in APS and DXM group than in CTX group (P<0.05), and increased to normal level at day10and14(P>0.05vs blank control group, P<0.05vs. G-CSF group). Conclusion:Dysfunction of releasing of "High quality" mature granulocytes was observed in rats7days after chemotherapy. APS could not only promote the proliferation and differentiation of bone marrow granulocytes, but also raise the expression of L-selectin, PSGL-1, CD11b/CD18and ADAM17to prompt the release of PMNL. Moreover, compared to G-CSF and DXM, APS could significantly improve the chemotacitic ability of mature BM granulocytes and peripheral blood PMNL after chemotherapy.