B-1a 细胞在肠道缺血再灌注损伤中的治疗潜力。
Therapeutic Potential of B-1a Cells in Intestinal Ischemia-Reperfusion Injury.
机构信息
Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, New York; Elmezzi Graduate School of Molecular Medicine, Manhasset, New York; Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, Manhasset, New York.
Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, New York.
出版信息
J Surg Res. 2021 Dec;268:326-336. doi: 10.1016/j.jss.2021.06.070. Epub 2021 Aug 13.
BACKGROUND
Acute mesenteric ischemia is a common surgical emergency. Restoration of blood flow is a critical objective of treating this pathology. However, many patients suffer from ischemia-reperfusion (I/R) injuries at the time of revascularization, requiring prolonged hospitalizations. B-1a cells are a subtype of B lymphocytes with roles in regulating inflammation and tissue injury by spontaneous release of natural IgM and IL-10. We hypothesized that treatment with B-1a cells protects mice from intestinal I/R.
METHODS
Mesenteric ischemia was induced in mice by placing a vascular clip on the superior mesenteric artery for 60 minutes. At the time of reperfusion, B-1a cells or PBS control were instilled into the peritoneal cavity (PerC) of mice. PerC lavage, blood, intestine, and lungs were collected 4 h after reperfusion. Serum organ injury and inflammatory markers such as ALT, AST, LDH, lactate, IL-6, as well as lung and gut histology and myeloperoxidase (MPO) were assessed.
RESULTS
In intestinal I/R, B-1a cell frequency and number in the PerC were significantly decreased compared to sham-operated mice. There was an increase in the serum levels of ALT, AST, LDH, lactate, and IL-6 when comparing the vehicle group with the sham group. These increases were significantly reduced in the B-1a cell treated group. B-1a cell treatment significantly decreased the intestine and lung injury scores as well as MPO content, compared to vehicle treated mice. B-1a cell treatment resulted in a reduction of apoptotic cells in these tissues. Serum IgM levels were decreased in intestinal I/R, while treatment with B-1a cells significantly increased their levels towards normal levels.
CONCLUSIONS
B-1a cell treatment at the time of mesenteric reperfusion ameliorates end organ damage and reduces systemic inflammation through the improvement of serum IgM levels. Preserving B-1a cells pool could serve as a novel therapeutic avenue in intestinal I/R injury.
背景
急性肠系膜缺血是一种常见的外科急症。恢复血流是治疗这种病理的关键目标。然而，许多患者在血管再通时会遭受缺血再灌注（I/R）损伤，需要延长住院时间。B-1a 细胞是 B 淋巴细胞的一个亚型，通过自发释放天然 IgM 和 IL-10 来调节炎症和组织损伤。我们假设 B-1a 细胞治疗可保护小鼠免受肠道 I/R 损伤。
方法
通过在肠系膜上动脉放置血管夹将肠系膜缺血诱导至小鼠，夹闭 60 分钟。在再灌注时，将 B-1a 细胞或 PBS 对照物注入小鼠的腹腔（PerC）。再灌注后 4 小时收集 PerC 灌洗液、血液、肠和肺。评估血清器官损伤和炎症标志物，如 ALT、AST、LDH、乳酸、IL-6，以及肺和肠道组织学和髓过氧化物酶（MPO）。
结果
在肠道 I/R 中，与假手术组相比，PerC 中的 B-1a 细胞频率和数量明显减少。与假手术组相比，在载体组中血清 ALT、AST、LDH、乳酸和 IL-6 的水平升高。在 B-1a 细胞治疗组中，这些升高明显降低。与载体治疗的小鼠相比，B-1a 细胞治疗显著降低了肠和肺损伤评分以及 MPO 含量。B-1a 细胞治疗导致这些组织中的凋亡细胞减少。在肠道 I/R 中，血清 IgM 水平降低，而用 B-1a 细胞治疗可显著将其水平提高至正常水平。
结论
在肠系膜再灌注时给予 B-1a 细胞治疗可改善终末器官损伤，并通过提高血清 IgM 水平来减轻全身炎症。保留 B-1a 细胞池可能成为肠道 I/R 损伤的新治疗途径。
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