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胎儿肝脏中的中性粒细胞储存池是出生后中性粒细胞激增的主要来源。

A Neutrophil Storage Pool in the Fetal Liver is the Principal Source of the Postnatal Neutrophil Surge.

作者信息

Ishiwata Ryo, Morimoto Yuji

机构信息

Department of Physiology, National Defense Medical College, Tokorozawa, Japan.

出版信息

FASEB J. 2025 Aug 15;39(15):e70921. doi: 10.1096/fj.202501613RR.

DOI:10.1096/fj.202501613RR
PMID:40767082
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12326356/
Abstract

Neutrophils, a key component of the innate immune system, undergo an acute surge in peripheral blood within the first day of life in mammalian neonates, yet the origin of this surge has remained elusive. In this study, we identify the fetal liver as the primary reservoir driving the postnatal neutrophil surge. In rat neonates, peripheral neutrophil counts rose significantly by 6 h after birth, a change not explained by a release from the bone marrow. Examination of fetal tissues revealed that neutrophils accumulate in the liver during late gestation in a granulocyte colony-stimulating factor (G-CSF)-dependent manner. Following delivery, both rat and mouse neonates displayed a rapid depletion of liver neutrophils within 12 h. Transcriptomic profiling of murine liver neutrophils at 3 h postpartum uncovered upregulation of Nos2 (encoding inducible nitric oxide synthase, iNOS). Pharmacological inhibition of NOS activity in rat pups significantly attenuated the magnitude of the postnatal neutrophil surge. Together, these findings reveal a previously unrecognized developmental program in which the fetal liver serves as the source of neutrophils that are mobilized immediately after birth, a mechanism that may underlie the diminished neutrophil response observed in preterm infants.

摘要

中性粒细胞是先天性免疫系统的关键组成部分，在哺乳动物新生儿出生后的第一天，外周血中的中性粒细胞会急剧增加，但其增加的来源一直难以确定。在本研究中，我们确定胎儿肝脏是驱动出生后中性粒细胞增加的主要储存库。在新生大鼠中，出生后6小时外周中性粒细胞计数显著上升，这种变化无法用骨髓释放来解释。对胎儿组织的检查显示，在妊娠后期，中性粒细胞以粒细胞集落刺激因子（G-CSF）依赖的方式在肝脏中积累。分娩后，大鼠和小鼠新生儿在12小时内肝脏中的中性粒细胞迅速减少。产后3小时对小鼠肝脏中性粒细胞进行转录组分析发现Nos2（编码诱导型一氧化氮合酶，iNOS）上调。对新生大鼠进行一氧化氮合酶活性的药理抑制可显著减弱出生后中性粒细胞增加的幅度。这些发现共同揭示了一个以前未被认识的发育程序，其中胎儿肝脏作为出生后立即被动员的中性粒细胞的来源，这一机制可能是早产儿中性粒细胞反应减弱的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/8f19037e8427/FSB2-39-e70921-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/f7e451db5121/FSB2-39-e70921-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/1116dccd5ee8/FSB2-39-e70921-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/4cc48971153f/FSB2-39-e70921-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/a542d233dba2/FSB2-39-e70921-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/d862ccc5bfdf/FSB2-39-e70921-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/cedcf4cf890b/FSB2-39-e70921-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/8f19037e8427/FSB2-39-e70921-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/f7e451db5121/FSB2-39-e70921-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/1116dccd5ee8/FSB2-39-e70921-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/4cc48971153f/FSB2-39-e70921-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/a542d233dba2/FSB2-39-e70921-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/d862ccc5bfdf/FSB2-39-e70921-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/cedcf4cf890b/FSB2-39-e70921-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54be/12326356/8f19037e8427/FSB2-39-e70921-g002.jpg

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本文引用的文献

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Exp Hematol. 2025 Aug;148:104798. doi: 10.1016/j.exphem.2025.104798. Epub 2025 May 9.
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Matrix-producing neutrophils populate and shield the skin.产生基质的中性粒细胞聚集并保护皮肤。
Nature. 2025 May;641(8063):740-748. doi: 10.1038/s41586-025-08741-5. Epub 2025 Mar 19.
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Spatiotemporal dynamics of fetal liver hematopoietic niches.胎儿肝脏造血微环境的时空动态变化
J Exp Med. 2025 Feb 3;222(2). doi: 10.1084/jem.20240592. Epub 2025 Jan 7.
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The neonatal liver hosts a spontaneously occurring neutrophil population, exhibiting distinct spatial and functional characteristics from adults.新生儿肝脏中存在自发出现的中性粒细胞群体，其具有与成人不同的独特空间和功能特征。
J Leukoc Biol. 2024 Nov 27;116(6):1352-1363. doi: 10.1093/jleuko/qiae082.
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Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis.胎肝巨噬细胞通过控制粒细胞生成来促进造血干细胞龛的形成。
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A novel Kit mutant rat enables hematopoietic stem cell engraftment without irradiation.一种新型 Kit 突变大鼠可实现造血干细胞植入而无需照射。
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An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life.IL-10/DEL-1 轴支持生命早期脓毒症中的粒细胞生成和存活。
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