Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205-3703, USA.
Cells. 2023 Jun 26;12(13):1719. doi: 10.3390/cells12131719.
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 Cl 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-Cl exposure. Plasma levels of SDF-1 and peripheral levels of CXCR4 in lung cells were higher in male vs. female mice post-Cl exposure. Myeloperoxidase (MPO) and elastase activity was significantly increased in leukocytes of male mice exposed to Cl. 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-Cl 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.
本研究旨在确定吸入性肺损伤的免疫反应是否存在性别差异。C57BL/6 小鼠暴露于氯气（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。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部迁移。因此，假设 SDF-1/CXCR4 信号转导增加介导了雄性中过度的免疫反应。在 Cl 暴露后，从小鼠收集血浆、血液白细胞和肺细胞。与 Cl 暴露后的雌性小鼠相比，雄性小鼠的血浆 SDF-1 水平和肺细胞外周 CXCR4 水平更高。暴露于 Cl 的雄性小鼠的白细胞髓过氧化物酶（MPO）和弹性蛋白酶活性显著增加。然后在存在或不存在 CXCR4 抑制剂 AMD3100（100 nM）的情况下，将肺细胞进行离体 SDF-1（100ng/mL）处理。与 Cl 暴露后的雌性小鼠相比，SDF-1 显著增加了雄性小鼠肺细胞的迁移、MPO 和弹性蛋白酶活性。AMD3100 减弱了这些作用，表明 SDF-1/CXCR4 信号转导的差异可能是导致吸入性肺损伤免疫反应中性别差异的原因。
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