Studying the Effects of Granulocyte-Macrophage Colony-Stimulating Factor on Fetal Lung Macrophages During the Perinatal Period Using the Mouse Model.
Studying the Effects of Granulocyte-Macrophage Colony-Stimulating Factor on Fetal Lung Macrophages During the Perinatal Period Using the Mouse Model.
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DOI：
10.3389/fped.2021.614209
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发表时间：
2021
影响因子：
2.6
通讯作者：
Kallapur SG
中科院分区：
文献类型：
--
作者：
Cheah FC;Presicce P;Tan TL;Carey BC;Kallapur SG
背景：粒细胞-巨噬细胞集落刺激因子（GM-CSF）是一种促炎细胞因子，在绒毛膜羊膜炎患者羊水中升高，在内毒素暴露的胎儿肺中升高。虽然GM-CSF在胎儿肺发育中起关键作用，但它刺激肺巨噬细胞并与支气管肺发育不良（BPD）的发展有关。产前GM-CSF如何导致肺巨噬细胞募集导致BPD有待进一步阐明。因此，我们采用转基因和敲除小鼠模型来研究GM-CSF对胎儿肺巨噬细胞的聚焦作用。方法：采用多西环素治疗后条件过表达的双转基因（BTg）小鼠和不表达GM-CSF的GM-CSF敲除（KO）小鼠，采用流式细胞术和免疫组织学方法比较BTg、KO和对照小鼠在产前和产后不同时间点肺巨噬细胞的发生和免疫表型。结果：在胎儿时期，与对照组相比，过度表达肺GM-CSF的BTg小鼠的肺CD68+巨噬细胞数量增加，这些巨噬细胞主要位于间质而不是肺泡间隙。积聚的肺巨噬细胞以CD11b+F4/80+为主，提示未成熟巨噬细胞。相反，GM-CSF小鼠的肺巨噬细胞虽然明显减少，但仍然存在。结论：在产前增加GM-CSF暴露可导致胎儿肺间质中未成熟巨噬细胞的积累。GM-CSF的缺失并没有阻止间质巨噬细胞的转移，而是延缓了间质巨噬细胞的转移。总之，这些结果表明，其他围产期因素可能参与调节胎儿肺发育中肺泡巨噬细胞的成熟。
Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pro-inflammatory cytokine that is increased in the amniotic fluid in chorioamnionitis and elevated in the fetal lung with endotoxin exposure. Although GM-CSF has a pivotal role in fetal lung development, it stimulates pulmonary macrophages and is associated with the development of bronchopulmonary dysplasia (BPD). How antenatal GM-CSF results in recruitment of lung macrophage leading to BPD needs further elucidation. Hence, we used a transgenic and knock-out mouse model to study the effects of GM-CSF focusing on the fetal lung macrophage. Methods: Using bitransgenic (BTg) mice that conditionally over-expressed pulmonary GM-CSF after doxycycline treatment, and GM-CSF knock-out (KO) mice with no GM-CSF expression, we compared the ontogeny and immunophenotype of lung macrophages in BTg, KO and control mice at various prenatal and postnatal time points using flow cytometry and immunohistology. Results: During fetal life, compared to controls, BTg mice over-expressing pulmonary GM-CSF had increased numbers of lung macrophages that were CD68+ and these were primarily located in the interstitium rather than alveolar spaces. The lung macrophages that accumulated were predominantly CD11b+F4/80+ indicating immature macrophages. Conversely, lung macrophages although markedly reduced, were still present in GM-CSF KO mice. Conclusion: Increased exposure to GM-CSF antenatally, resulted in accumulation of immature macrophages in the fetal lung interstitium. Absence of GM-CSF did not abrogate but delayed the transitioning of interstitial macrophages. Together, these results suggest that other perinatal factors may be involved in modulating the maturation of alveolar macrophages in the developing fetal lung.
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影响因子：
32.4
作者：
Shibata, Y;Berclaz, PY;Trapnell, BC
通讯作者：
Trapnell, BC
DOI：
10.1152/ajplung.1997.273.4.l715
发表时间：
1997-10-01
影响因子：
4.9
作者：
Reed, JAH;Rice, WR;Whitsett, JA
通讯作者：
Whitsett, JA
DOI：
10.1152/ajplung.00216.2003
发表时间：
2003-11-01
影响因子：
4.9
作者：
Bonfield, TL;Raychaudhuri, B;Thomassen, MJ
通讯作者：
Thomassen, MJ
影响因子：
5.6
作者：
HAMILTON, JA;STANLEY, ER;SHADDUCK, RK
通讯作者：
SHADDUCK, RK
肺泡巨噬细胞从胎儿单核细胞中发展，这些单核细胞在生命的第一周通过GM-CSF分化为长寿命细胞。
DOI：
10.1084/jem.20131199
发表时间：
2013-09-23
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guilliams M;De Kleer I;Henri S;Post S;Vanhoutte L;De Prijck S;Deswarte K;Malissen B;Hammad H;Lambrecht BN
通讯作者：
Lambrecht BN