3.6. HMGB1/CXCL12 complex in the serum of PD patients.
Since the HMGB1/CXCL12 complex plays an important role in the infiltration of monocytes/macrophages and T cells in a mouse model. Previously, it has also been reported that the up-regulation of CXCL12 and HMGB1 in PD patients may be related to the course of PD(Li et al. , 2019; Santoro et al. , 2016). However, there is no evidence whether the HMGB1/CXCL12 complex exists in PD patients. We detected the serum levels of HMGB1 and CXCL12 in 20 PD patients and 20 healthy people in the same age range. The results showed that PD patients had significantly higher serum HMGB1 and CXCL12 levels (Fig. 6A, B). Moreover, PD patients showed a significant positive correlation between HMGB1 and CXCL12 levels, which highly suggested a possible combination between the two (Fig. 6C). Serum co-immunoprecipitation experiments also confirmed the existence of the HMGB1/CXCL12 complex (Fig. 6D). There is a certain relationship between PD and age. The degeneration of dopaminergic neurons when aging is one of the causes of PD. When we analyzed the correlation between HMGB1 and CXCL12 in PD patients and age, a significant negative correlation was observed between CXCL12 and PD patients’ age, while HMGB1 levels were not significantly correlated with age in PD patients (Fig. 6E, F). Then, we used magnetic beads to sort CD3+ T cells and CD14+monocytes from the peripheral blood of PD patients, and the results of co-immunoprecipitation showed that CXCR4 of CD14 monocytes bound to both HMGB1 and CXCL12 (Fig. 6G). And immunofluorescence results showed that HMGB1 and CXCL12 co-localized with CXCR4 on the surface of CD3+ T cells and CD14+ monocytes (Fig. 6H). These results of patients may suggest that treatment targeting HMGB1/CXCL12-CXCR4 may be more suitable for patients with earlier Parkinson’s disease.