Protective Effects Of Platelet Factor 4 (PF4) On Bone Marrow Stromal Cells Of Acute Radiation Injury In Mice

Up to now radiotherapy is still one of methods to treat malignant tumors. But patients are likely to experience acute or chronic side effects resulting from radiotherapy. The hematopoietic functional disorders are the basic pathological changes of acute radiation damage, which involve in hematopoietic stem/progenitor cells and stromal cells injury. Hematopoietic inductive microenvironment, especially bone marrow stromal cell, is important to regulating and sustaining hematopoiesis. Stromal cells cooperate with extra-cellular matrix to regulate hematopoietic cells proliferation and differentiation by secreting a lot of chemokines and expressing adhesive molecules. The structural and functional integrity of stromal cells are also important to stabilization of keeping physiological hematopoiesis, especially in irritable condition.Platelet factor 4 (PF4) is a 7.8-kDa protein synthesized by megakaryocytes, stored in a-granules as a noncovalent tetrmer and released from activated platelets. It is heparin combinative peptides, which has abilities of neutralizing heparin, chemotactic inflammation, antiangiogenesis, inhibiting megakaryocytes development. In recent recearches, PF4 , as negative regulator of bone marrow cells proliferation can reversibly inhibit the proliferation of the normal hematipoietic stem/progenitor cells, decrease their sensitivity to the damage of radiotherapy and chemotherapy, but it has not influence on the tumor cells. Therefore, PF4 can keep hemaotopoietic stem/progenotor cells from injury of radiation and cytotoxic reagent. The tumor patients who received radiotherapy and chemotherapy in combination with PF4 could decrease hematopoietic damage and inhibit the growth of tumors through inhibiting angiogenesis. In this study, for the first time, we culture in vitro bone marrow stromal cells from acute radiated injury mice, observe protective effects of PF4, discuss the protective mechanism of PF4 on radiation injury.AIM: To investigate the protective effects of platelet factor 4(PF4) on bone marrow stromal cells (BMSCs) of radiated mice and protective mechanism of radiation injury on hematopoietic cells. METHODS: Forty male mice were randomly divided four groups and two of groups were exposed whole-bodily to 5.0 Gy ~60Co γ -rays. The mice were treated with PF4(50 μ g/ kg), twice ip , at an interval of 6 h and 20 h, after the second injection they were irradiated. BMSCs, cultured in vitro after radiation, were analyzed cell cycle , apoptosis and content off DNA by FCM after ten days culture. The number of CFU-F was counted after 3 days, 7 days, and 14 days culture respectively. The spleen/ thymus vs body...