小柯机器人

科学家发现一条对感染后修复至关重要的单核细胞-瘦素-血管生成途径
2022-08-13 23:46

加拿大卡尔加里大学Paul Kubes、Justin F. Deniset等研究人员合作发现一条对感染后修复至关重要的单核细胞-瘦素-血管生成途径。该研究于2022年8月10日在线发表于国际一流学术期刊《自然》。

研究人员使用涂有金黄色葡萄球菌的异物,并对从皮肤感染到伤口解决的时间进行成像,表明单核细胞和中性粒细胞在低剂量感染时被招募的数量相似,但在高剂量感染时则不然,并形成一种定位模式,即单核细胞围绕感染部位,而中性粒细胞则浸润在其中。单核细胞对细菌清除没有贡献,但转化为巨噬细胞,在感染后持续数周,调节下皮脂肪细胞的扩张和脂肪因子激素瘦素的产生。在被感染的单核细胞缺陷的小鼠中,皮下持续增厚,瘦素水平升高,促使功能失调的血脉过度生长,延迟愈合,出现增厚的疤痕。与瘦素功能相对立的Ghrelin由单核细胞局部产生,并减少血管过度生长,改善感染后的愈合。总之,研究人员发现单核细胞通过调节瘦素水平和伤口修复过程中的血管再生发挥着细胞变阻器的作用。
 
据了解,在感染期间,炎症单核细胞被认为是根除细菌的关键,但这很难与每一个迁移到受影响组织的单核细胞所招募的大量中性粒细胞相协调,而且中性粒细胞的杀微生物功能更为强大。然而,与中性粒细胞不同,单核细胞有能力转化为特定情况下的巨噬细胞,这些巨噬细胞可能具有超越感染控制的关键功能。
 
附:英文原文
 
Title: A monocyte–leptin–angiogenesis pathway critical for repair post-infection

Author: Kratofil, Rachel M., Shim, Hanjoo B., Shim, Raymond, Lee, Woo Yong, Labit, Elodie, Sinha, Sarthak, Keenan, Catherine M., Surewaard, Bas G. J., Noh, Ji Yeon, Sun, Yuxiang, Sharkey, Keith A., Mack, Matthias, Biernaskie, Jeff, Deniset, Justin F., Kubes, Paul

Issue&Volume: 2022-08-10

Abstract: During infection, inflammatory monocytes are thought to be key for bacterial eradication, but this is hard to reconcile with the large numbers of neutrophils that are recruited for each monocyte that migrates to the afflicted tissue, and the much more robust microbicidal functions of the neutrophils. However, unlike neutrophils, monocytes have the capacity to convert to situationally specific macrophages that may have critical functions beyond infection control1,2. Here, using a foreign body coated with Staphylococcus aureus and imaging over time from cutaneous infection to wound resolution, we show that monocytes and neutrophils are recruited in similar numbers with low-dose infection but not with high-dose infection, and form a localization pattern in which monocytes surround the infection site, whereas neutrophils infiltrate it. Monocytes did not contribute to bacterial clearance but converted to macrophages that persisted for weeks after infection, regulating hypodermal adipocyte expansion and production of the adipokine hormone leptin. In infected monocyte-deficient mice there was increased persistent hypodermis thickening and an elevated leptin level, which drove overgrowth of dysfunctional blood vasculature and delayed healing, with a thickened scar. Ghrelin, which opposes leptin function3, was produced locally by monocytes, and reduced vascular overgrowth and improved healing post-infection. In sum, we find that monocytes function as a cellular rheostat by regulating leptin levels and revascularization during wound repair.

DOI: 10.1038/s41586-022-05044-x

Source: https://www.nature.com/articles/s41586-022-05044-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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