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小鼠B淋巴细胞缺陷通过诱导中性粒细胞增多导致血管功能障碍。

B Lymphocyte-Deficiency in Mice Causes Vascular Dysfunction by Inducing Neutrophilia.

作者信息

Xia Ning, Hasselwander Solveig, Reifenberg Gisela, Habermeier Alice, Closs Ellen I, Mimmler Maximilian, Jung Rebecca, Karbach Susanne, Lagrange Jérémy, Wenzel Philip, Daiber Andreas, Münzel Thomas, Hövelmeyer Nadine, Waisman Ari, Li Huige

机构信息

Department of Pharmacology, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany.

Institute for Molecular Medicine, Johannes Gutenberg University Medical Center, 55131 Mainz, Germany.

出版信息

Biomedicines. 2021 Nov 14;9(11):1686. doi: 10.3390/biomedicines9111686.

Abstract

B lymphocytes have been implicated in the development of insulin resistance, atherosclerosis and certain types of hypertension. In contrast to these studies, which were performed under pathological conditions, the present study provides evidence for the protective effect of B lymphocytes in maintaining vascular homeostasis under physiological conditions. In young mice not exposed to any known risk factors, the lack of B cells led to massive endothelial dysfunction. The vascular dysfunction in B cell-deficient mice was associated with an increased number of neutrophils in the circulating blood. Neutrophil depletion in B cell-deficient mice resulted in the complete normalization of vascular function, indicating a causal role of neutrophilia. Moreover, vascular function in B cell-deficient mice could be restored by adoptive transfer of naive B-1 cells isolated from wild-type mice. Interestingly, B-1 cell transfer also reduced the number of neutrophils in the recipient mice, further supporting the involvement of neutrophils in the vascular pathology caused by B cell-deficiency. In conclusion, we report in the present study the hitherto undescribed role of B lymphocytes in regulating vascular function. B cell dysregulation may represent a crucial mechanism in vascular pathology.

摘要

B淋巴细胞与胰岛素抵抗、动脉粥样硬化及某些类型的高血压的发展有关。与这些在病理条件下进行的研究不同,本研究为B淋巴细胞在生理条件下维持血管稳态的保护作用提供了证据。在未暴露于任何已知风险因素的年轻小鼠中,B细胞的缺失导致大量内皮功能障碍。B细胞缺陷小鼠的血管功能障碍与循环血液中嗜中性粒细胞数量增加有关。B细胞缺陷小鼠中的嗜中性粒细胞耗竭导致血管功能完全恢复正常,表明嗜中性粒细胞增多具有因果作用。此外,通过从野生型小鼠分离的天然B-1细胞的过继转移,可以恢复B细胞缺陷小鼠的血管功能。有趣的是,B-1细胞转移也减少了受体小鼠中嗜中性粒细胞的数量,进一步支持了嗜中性粒细胞参与B细胞缺陷引起的血管病理过程。总之,我们在本研究中报告了B淋巴细胞在调节血管功能方面迄今未被描述的作用。B细胞失调可能是血管病理的关键机制。

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