Sex-Based Disparities in Leukocyte Migration and Activation in Response to Inhalation Lung Injury: Role of SDF-1/CXCR4 Signaling.

Sex-Based Disparities in Leukocyte Migration and Activation in Response to Inhalation Lung Injury: Role of SDF-1/CXCR4 Signaling.
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基于性别的白细胞迁移和激活对吸入肺损伤的差异:SDF-1/CXCR4信号的作用。

DOI:
10.3390/cells12131719
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发表时间:
2023-06-26
期刊:
影响因子:
6
通讯作者:
Aggarwal, Saurabh
Aggarwal, Saurabh
中科院分区:
生物学2区
文献类型:
--
作者:
Chatterjee, Tanima;Lewis, Terry L. L.;Arora, Itika;Gryshyna, Anastasiia E. E.;Underwood, Lilly;Masjoan Juncos, Juan Xavier;Aggarwal, Saurabh

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该研究的目的是确定吸入性肺损伤的免疫反应是否存在性别相关差异。C57BL/6小鼠暴露于Cl2气体(500 ppm, 15、20或30分钟)。结果表明,雄性小鼠的死亡率和肺损伤率高于雌性小鼠。趋化因子配体C-X-C基序趋化因子12 (CXCL12),也称为基质衍生因子-1 (SDF-1)与肺细胞上的C-X-C趋化因子受体4 (CXCR4)结合,促进白细胞从循环向肺的迁移。因此,假设升高的SDF-1/CXCR4信号介导了男性过度的免疫反应。收集暴露于cl2后小鼠的血浆、血液白细胞和肺细胞。暴露于cl2后,雄性小鼠的血浆中SDF-1水平和外周肺细胞中CXCR4水平高于雌性小鼠。暴露于Cl2的雄性小鼠白细胞中髓过氧化物酶(MPO)和弹性酶活性显著增加。然后在CXCR4抑制剂AMD3100 (100 nM)存在或不存在的情况下,用SDF-1 (100 ng/mL)体外处理肺细胞。暴露于cl2后,SDF-1显著增加了雄性小鼠与雌性小鼠细胞的迁移、MPO和弹性酶活性。AMD3100减弱了这些作用,提示不同的SDF-1/CXCR4信号可能导致吸入性肺损伤免疫反应的性别差异。
The aim of the study was to determine whether sex-related differences exist in immune response to inhalation lung injury. C57BL/6 mice were exposed to Cl2 gas (500 ppm for 15, 20, or 30 min). Results showed that male mice have higher rates of mortality and lung injury than females. The binding of the chemokine ligand C-X-C motif chemokine 12 (CXCL12), also called stromal-derived-factor-1 (SDF-1), to the C-X-C chemokine receptor type 4 (CXCR4) on lung cells promotes the migration of leukocytes from circulation to lungs. Therefore, the hypothesis was that elevated SDF-1/CXCR4 signaling mediates exaggerated immune response in males. Plasma, blood leukocytes, and lung cells were collected from mice post-Cl2 exposure. Plasma levels of SDF-1 and peripheral levels of CXCR4 in lung cells were higher in male vs. female mice post-Cl2 exposure. Myeloperoxidase (MPO) and elastase activity was significantly increased in leukocytes of male mice exposed to Cl2. Lung cells were then ex vivo treated with SDF-1 (100 ng/mL) in the presence or absence of the CXCR4 inhibitor, AMD3100 (100 nM). SDF-1 significantly increased migration, MPO, and elastase activity in cells obtained from male vs. female mice post-Cl2 exposure. AMD3100 attenuated these effects, suggesting that differential SDF-1/CXCR4 signaling may be responsible for sex-based disparities in the immune response to inhalation lung injury.
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