Histopathological Correlations between Mediastinal Fat-Associated Lymphoid Clusters and the Development of Lung Inflammation and Fibrosis following Bleomycin Administration in Mice.
Histopathological Correlations between Mediastinal Fat-Associated Lymphoid Clusters and the Development of Lung Inflammation and Fibrosis following Bleomycin Administration in Mice.
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DOI：
10.3389/fimmu.2018.00271
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发表时间：
2018
影响因子：
7.3
通讯作者：
Kon Y
中科院分区：
文献类型：
--
作者：
Elewa YHA;Ichii O;Takada K;Nakamura T;Masum MA;Kon Y
博莱霉素（BLM）已被报道可诱导人类和小鼠的肺部炎症和纤维化，并显示出遗传易感性。有趣的是，C57 BL/6（B6）小鼠在健康条件下具有显著的纵隔脂肪相关淋巴簇（MFALC），并且在BLM施用后显示出对肺纤维化发展的易感性。然而，肺部病变进展的发病机制及其与MFALC形态学的相关性仍有待阐明。为了研究B6小鼠中MFALC结构与肺损伤之间的相关性，在单次50 μL鼻内（i.n.）BLM硫酸盐（5 mg/kg）（BLM组）或磷酸盐缓冲盐水（对照组）滴注。石蜡切片Masson三色染色检测肺纤维化程度，并检测不同冻存肺组织中Col 1a 1、Col 3a 1和Acta 2 mRNA表达水平。此外，进行CD 3、B220、Iba 1、Gr 1、BrdU、LYVE-1和外周淋巴结地址素（PNAd）的免疫组织化学，以检测T细胞和B细胞、巨噬细胞、粒细胞、增殖细胞、淋巴管（LV）和高内皮微静脉（HEV）。我们发现与对照组相比，BLM组的MFALCs更丰富。BLM组在给药后7 d出现肺部炎症，细胞浸润严重，21 d出现胶原沉积（MT），Col 1a 1和Col 3a 1表达增加。在BLM组的MFALC和肺中观察到大量的免疫细胞、增殖细胞、HEV和LV。有趣的是，在BLM组的肺中观察到PNAd + HEV，但在对照组中未观察到。此外，BLM组的MFALC和肺中发现了大量的Gr 1+多形核和单核样环细胞。有趣的是，流式细胞术分析显示BLM组的MFALC内B细胞群显著增加，表明炎症后B细胞的潜在增殖诱导。此外，在肺和MFALC中的这些免疫细胞的定量参数之间观察到显著的正相关。因此，我们认为MFALCs和HEV在肺部疾病，特别是炎症性肺部疾病的进展中可能发挥重要作用。
Bleomycin (BLM) has been reported to induce lung inflammation and fibrosis in human and mice and showed genetic susceptibility. Interestingly, the C57BL/6 (B6) mice had prominent mediastinal fat-associated lymphoid cluster (MFALCs) under healthy condition, and showed susceptibility to development of lung fibrosis following BLM administration. However, the pathogenesis of lung lesion progression, and their correlation with MFALC morphologies, remain to be clarified. To investigate the correlations between MFALC structures and lung injuries in B6 mice, histopathological examination of mediastinal fat tissues and lungs was examined at 7 and 21 days (d) following a single 50 μL intranasal (i.n.) instillation of either BLM sulfate (5 mg/kg) (BLM group) or phosphate-buffered saline (control group). The lung fibrosis was examined by Masson’s trichrome (MT) stain of paraffin sections and mRNA expression levels of Col1a1, Col3a1, and Acta2 in different frozen lung samples. Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1, BrdU, LYVE-1, and peripheral node addressin (PNAd) was performed to detect T- and B-cells, macrophages, granulocytes, proliferating cells, lymph vessels (LVs), and high endothelial venules (HEVs). We found that MFALCs were more abundant in the BLM group as compared to the control group. The lung of BLM group developed pneumonitis with severe cellular infiltrations at 7 days and significant collagen deposition (MT) and higher expression of Col1a1, and Col3a1 at 21 days post-administration. Numerous immune cells, proliferating cells, HEVs, and LVs were observed in both MFALCs and lungs of the BLM group. Interestingly, PNAd + HEVs were observed in the lungs of the BLM group, but not the control group. Moreover, numerous Gr1 + polymorphonuclear and mononuclear-like ring cells were found in the MFALCs and lungs of the BLM group. Interestingly, flow cytometric analysis revealed a significant increase of B-cell populations within the MFALCs of BLM group suggesting a potential proliferative induction of B-cells following inflammation. Furthermore, significant positive correlations were observed between quantitative parameters of these immune cells in both the lungs and MFALCs. Thus, we suggest a potentially important role for MFALCs and HEVs in the progression of lung disease, especially in inflammatory lung disease.
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DOI：
10.1084/jem.20162152
发表时间：
2017-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Misharin AV;Morales-Nebreda L;Reyfman PA;Cuda CM;Walter JM;McQuattie-Pimentel AC;Chen CI;Anekalla KR;Joshi N;Williams KJN;Abdala-Valencia H;Yacoub TJ;Chi M;Chiu S;Gonzalez-Gonzalez FJ;Gates K;Lam AP;Nicholson TT;Homan PJ;Soberanes S;Dominguez S;Morgan VK;Saber R;Shaffer A;Hinchcliff M;Marshall SA;Bharat A;Berdnikovs S;Bhorade SM;Bartom ET;Morimoto RI;Balch WE;Sznajder JI;Chandel NS;Mutlu GM;Jain M;Gottardi CJ;Singer BD;Ridge KM;Bagheri N;Shilatifard A;Budinger GRS;Perlman H
通讯作者：
Perlman H
影响因子：
3.1
作者：
Manali ED;Moschos C;Triantafillidou C;Kotanidou A;Psallidas I;Karabela SP;Roussos C;Papiris S;Armaganidis A;Stathopoulos GT;Maniatis NA
通讯作者：
Maniatis NA
影响因子：
16.6
作者：
Jackson-Jones, Lucy H.;Duncan, Sheelagh M.;Magalhaes, Marlene S.;Campbell, Sharon M.;Maizels, Rick M.;McSorley, Henry J.;Allen, Judith E.;Benezech, Cecile
通讯作者：
Benezech, Cecile
影响因子：
16.6
作者：
Buscher, Konrad;Wang, Huiyu;Song, Jian
通讯作者：
Song, Jian
影响因子：
4
作者：
Liu MH;Lin AH;Ko HK;Perng DW;Lee TS;Kou YR
通讯作者：
Kou YR