The Expression Level Of Gas6 And Its Receptors Of Bone Marrow In Patients With Chronic Mountain Sickness

Background Chronic mountain sickness(CMS) is a clinical syndrome characterized by excessive erythrocytosis and hypoxemia,which is caused by maladaptation to chronic exposure to a high-altitude hypoxic environment and occurs among some individuals inhabiting plateau. The pathogenesis of red blood cells excessive accumulation in CMS is still unclear. Researches suggested that there exists an erythropoietin(EPO) independency regulation mechanism. In recent years, researches have showed that hematopoietic tissue, hematopoietic cells and bone marrow stromal cells express Gas6 protein and all members of the TAM receptors, which indicate that Gas6- TAM receptors are involved in hematopoietic regulation. Another study shows that Gas6, Axl receptor together with HIF- 1 α were expressed in prostate cancer tissues, hypoxia inhanced the signal transduction of Gas6- Axl receptor. On the whole,Gas6- TAM receptor system play an important role in the regulation of erythropoiesis, and which may be affected by hypoxia. So on the basis of the pathogenesis of CMS and the main pathological physiology characteristic of hematological system, we put forward a hypothesis that the expression level and activity of Gas6- TAM receptor system components of circulation blood and/or bone marrow tissue/cells in CMS patients is abnormal, which may be related with excessive erythrocytosis, especially through paracrine/autocrine mechanism, Gas6 in local bone marrow promote erythrocytosis,and then develop polycythemia.Objective To detect the parameter of HB,HCT,the concentration of Gas6 in bone marrow and blood by ELISA and the m RNA expression of Axl, Mer receptor and Gas6 ligand m RNA in bone marrow MNC by RT-PCR.To calculate Gas6 concentrations of bone marrow-blood gradient when it is necessary.Make the comparison analysis and correlation analysis of the detection indexs above.To analyzeGas6 of bone marrow and peripheral blood cells in CMS patients,also its receptors,whether or not to influence polycythemia.Methods The concentration of Gas6 protein in bone marrow and blood were determined by ELISA method, and the marrow-blood concentration gradient was calculated when it is necessary. The m RNA expression of Axl, Mer receptor and Gas6 ligand in bone marrow MNC were detected by RT-PCR. These parameters mentioned above were compared between CMS group and control group, and the correlations among detection index, HB were analyzed.Result ① the m RNA expression level of Axl, Mer, Gas6 in bone marrow and Gas6 protein in bone marrow and peripheral blood: The expression level of Mer in CMS[0.39(0.31)%] is lower than the control group[0.97(0.92)%] having significance(P < 0.05).However,there were no significance( P > 0.05) of the expression level of Axl m RNA,Gas6 m RNA, BM Gas6 Protein and PB Gas6 Protein between CMS{ respectively [( 0.39±0.45) %], [( 0.44±0.36) %],[( 35.64±9.12) pg /m L],[( 35.27±7.43) pg /m L] }and the control group { respectively[(0.64±0.55)%],[(0.58±0.34)%],[(38.94±5.99)pg /m L],[(34.21±9.56)pg /m L]}.Morever, there was no significance( P > 0.05) of the expression level of Gas6 Protein in CMS between BM[(35.64±9.12)pg /m L] and PB [(35.27±7.43)pg /m L],the same as the control group{ respectively[( 35.64±9.12) pg /m L],[(34.21±9.56)pg /m L] }.② There were significance of Sa O2,HB,HCT between CMS{(89.42±4.25)%,(224.75±16.15)g/L,(69.04±6.70)%} and the control group{(96.86±0.78)%,(138.00±17.21)g/L,(39.90±2.24)%},but of no significance in Age{respectively[( 47.83±8.11) years],[( 47.33±14.21) years] }. ③ All of parameters in CMS group and control group were found no relationships with HB,(P values were > 0.05).There were no relationships among the m RNA expression level of Axl, Mer, Gas6 in bone marrow and Gas6 protein in bone marrow and peripheral blood(P values were > 0.05).Conclusion ① Gas6 and its receptors Axl and Mer are expressed in both CMSgroup and control group,but the expression level of Mer is lower than the control group. ② Gas6 is expressed in BM and PB in both CMS and controls,but no significance.And the paracrine/autocrine mechanism of Gas6 in local bone marrow is not found. ③ All of parameters in CMS group and control group are found no relationships with HB,also there are no relationships among the m RNA expression level of Axl, Mer, Gas6 in bone marrow and Gas6 protein in bone marrow and peripheral blood.