梯度氧浓度下多形核白细胞的趋化特性与机制

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目的探讨梯度氧浓度下大鼠多形核白细胞的趋化特性与机制。方法用ibidi 6通道细胞趋化板观察白细胞在梯度下氧浓度的趋化方向。用48孔趋化小室趋化板观察趋化因子作用于白细胞后在缺氧条件下的趋化能力以及白细胞缺氧培养上清的趋化能力,结合甲酰肽受体拮抗剂,分析缺氧白细胞上清中甲酰肽受体激动剂水平。用免疫印迹检测多形核白细胞不同缺氧时间(0、3、6、12、24 h)或趋化因子作用后葡萄糖转运体1的表达。结果在梯度氧浓度下,白细胞趋化呈现明显的方向性,白细胞向梯度氧浓度的低氧侧迁移。细胞缺氧培养上清诱导的趋化反应显著高于常氧培养上清,用甲酰肽受体特异性拮抗剂可显著削弱这一反应。用甲酰肽受体激动剂预处理或缺氧预处理显著增强白细胞在缺氧条件下对血清的趋化反应,并剂量依赖性地上调白细胞葡萄糖转运体1表达,显著增强在缺氧条件下的葡萄糖摄取率。结论多形核白细胞逆梯度氧浓度趋化,其机制可能与低氧促进靠近低氧侧的细胞释放甲酰肽受体激动剂等趋化因子有关。这些趋化因子在诱导趋化的同时提高白细胞葡萄糖摄取能力,从而提高白细胞无氧代谢能力或省氧能力。 Objective To investigate the chemotaxis and mechanism of rat polymorphonuclear leukocytes under gradient oxygen concentration. Methods The ibidi 6-channel chemotactic plate was used to observe the chemotactic orientation of leukocyte oxygen concentration in a gradient. 48 chemotactic chemotaxis chambers were used to observe chemotactic ability of chemotactic cells in leukocytes chemotactic ability under hypoxic conditions and leukocyte hypoxia culture supernatants chemotactic capacity combined with formyl peptide receptor antagonist, analysis of hypoxia Formyl peptide receptor agonist levels in leukocyte supernatant. Immunoblotting was used to detect the expression of GLUT-1 after different time of hypoxia (0, 3, 6, 12, 24 h) or chemokines. Results Under the gradient oxygen concentration, leukocyte chemotaxis showed obvious directionality and leukocytes migrated to the hypoxia side of the gradient oxygen concentration. The chemotactic response induced by hypoxic culture supernatant was significantly higher than that of normoxic culture supernatants, which was significantly attenuated by the specific antagonist of formyl peptide receptor. Pretreatment with formyl peptide receptor agonists or hypoxic preconditioning significantly enhanced the chemotactic response of leukocytes to serum under hypoxic conditions and upregulated the expression of leukocyte glucose transporter 1 in a dose-dependent manner, Glucose uptake rate. Conclusions The chemotaxis of chemosensitive reverse-gradient oxygen polymorphisms in polymorphonuclear leukocytes may be related to the release of chemokines such as formyl peptide receptor agonists by hypoxia-stimulated cells near the hypoxic side. These chemokines increase leukocyte glucose uptake while inducing chemotaxis, thereby improving leukocyte anaerobic metabolism or oxygen saving.
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