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2018 ; 9
(ä): 271
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English Wikipedia
Histopathological Correlations between Mediastinal Fat-Associated Lymphoid
Clusters and the Development of Lung Inflammation and Fibrosis following
Bleomycin Administration in Mice
#MMPMID29497425
Elewa YHA
; Ichii O
; Takada K
; Nakamura T
; Masum MA
; Kon Y
Front Immunol
2018[]; 9
(ä): 271
PMID29497425
show ga
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??L 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.