Abstract
Acute lung injury caused by cardiopulmonary bypass (CPB) is characterized by massive neutrophil migration to the lungs. Neutrophil migration may be closely related to stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor Type 4 (CXCR4) axis activation, which plays an essential role in modulating the trafficking of neutrophils. We investigated the changes in the expression of SDF-1/CXCR4 axis components before and after CPB as well as the role of the axis in driving the migration of neutrophils in patients with congenital heart disease. Fifteen children undergoing elective open-heart surgery under CPB (CPB group) and 15 children undergoing minimally invasive ultrasound-guided closure of a ventricular septal defect (control group) were enrolled in this non-randomized clinical trial. Neutrophil CXCR4 expression was evaluated using quantitative reverse transcription polymerase chain reaction and flow cytometry. An enzyme-linked immunosorbent assay was used to measure plasma SDF-1 levels. The migration characteristics of neutrophils under 8 different combinations designated A-H were assayed with and without a specific CXCR4 antagonist, AMD3100, to evaluate the functional significance of the SDF-1/CXCR4 axis. Both CXCR4 gene and protein expressions were elevated in the CPB group compared with the control group after CPB (0.81 ± 0.55 vs 1.76 ± 1.32; P < 0.05, 1.96 ± 0.86 vs 2.65 ± 0.79; P < 0.05), and plasma SDF-1 levels were also increased in the former compared with the latter (197.84 ± 19.96 pg/ml vs 539.13 ± 99.83 pg/ml; P < 0.05). The in vitro experiments showed that plasma isolated post-CPB exhibited the strongest chemotactic effect on neutrophils. The CPB group showed a higher chemotaxis index, which serves as a marker for the effects of plasma on neutrophils, than that for the control group after CPB (37.38 ± 9.39 vs 13.61 ± 2.59; P < 0.05). In addition, the CXCR4 antagonist AMD3100 significantly abrogated the increase in neutrophil migration in the CPB group. Exposure to CPB, which activates the SDF-1/CXCR4 axis, using an antagonist to prevent neutrophil trafficking, may be a beneficial therapy for the related complications.
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