The Mechanism Of SDF-1/CXCR4 Axis In Driving Neutrophil Migration Caused By Cardiopulmonary Bypass On Children

Objective: To investigate the changes of the expression of the SDF-1/CXCR4 axis in congenital heart disease patients before and after CPB,and its role in driving neutrophil migration.Methods: Fifteen children undergoing elective open-heart surgery for CPB(CPB group)and 15 children undergoing minimally invasive closure of ventricular septal defect(VSD)with ultrasound-guided closure(control group)were enrolled.The blood samples of children undergoing cardiac surgery were obtained before and after CPB/surgery.We evaluated the expression of CXCR4 using RT-q PCR and flow cytometry.The enzyme-linked immunosorbent assay was taken to measure plasma stromal cell-derived factor-1(SDF-1)levels.The in vitro chemotaxis of neutrophils to plasma harvested from patients before and after CPB/surgery was assayed to evaluate the functional significance of the SDF-1/CXCR4 axis.Results: In CPB group,both CXCR4 gene and protein expression were elevated after CPB(p < 0.05),and showed higher levels when compared with the control group after CPB/surgery(p < 0.05),plasma SDF-1 levels were found to rise in a similar fashion(p < 0.05).In vitro experiments,the chemotaxis response between plasma and neutrophils had no significant changes among four treatment protocols in the control group.However,plasma isolated from post-CPB showed the strongest chemotactic effect to the neutrophils from post-CPB.The CPB group showed a higher chemotactic index of treatment D compared with the control group(p < 0.05).In addition,the CXCR4 antagonist AMD3100 led to abrogation of neutrophil migration increasing in CPB group.Conclusion: Exposure to CPB leads to an increase in both plasma SDF-1 levels and CXCR4 expression,positively associated with the enhanced chemotaxis of neutrophils in response to CPB,suggesting an essential role for this SDF-1/CXCR4 axis in modulating neutrophils recruitment.