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Neutrophil chemotaxis dysfunction and potential mechanisms in diabetes mellitus#br# |
LI Linbin, WU Mian, YANG Yunxi, SHAO Yiming, LIU Lu, HUANG Jiamin, SUN Bingwei |
(Burn and Trauma Center, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou Jiangsu 215004, China)
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Abstract Objective: To investigate whether the chemotactic function of neutrophils in type 2 diabetes is impaired and its underlying mechanism. Methods: According to the WHO diagnostic criteria, a total of 45 patients with diagnosed type 2 diabetes and 45 healthy controls of the same age were recruited. The tested neutrophils were all collected from the peripheral blood of the subjects′ cubital veins. The chemotactic function of neutrophils in the two groups was detected by the modified chemotaxis method under agarose, and the expression level of P2X1 receptor on the surface of neutrophil membrane was detected by flow cytometry and immunofluorescence. In the intervention experiments, the normal neutrophils were stimulated by diluted plasma of patients with type 2 diabetes or healthy controls (90%, 20%), media with different glucose contents (5, 12 and 25 mmol/L), end products of glycation (0.5,1, 2 and 4 mmol/L) and palmitic acid (50, 100 and 200 μmol/L) and the chemotaxis were detected. Results: Compared with healthy controls, the chemotactic function of neutrophils type 2 diabetes was significantly reduced (P<0.001), and the expression of P2X1 receptors increased (P<0.001). There was a significantly negative correlation between them (r=-0.60, P<0.001). Compared with the control group, the patients′ highconcentration plasma significantly inhibited the chemotactic function of neutrophils (P<0.001). Each concentration of glycation end products and glucose was not significantly inhibited neutrophils chemotaxis function (P>0.05). While high concentrations of palmitic acid (200 μmol/L) significantly inhibited the chemotaxis of neutrophils (P<0.05), the expression of P2X1 receptors on the cell surface increased (P<0.05), and there was a significantly negative correlation (r=-0.67, P<0.05) between them. Conclusion: The chemotaxis of neutrophils is impaired in type 2 diabetes, and high concentrations of palmitic acid impairs the chemotaxis of neutrophils through P2X1 receptors.
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Received: 12 October 2021
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