Fully automated estimation of the mean linear intercept in histopathology images of mouse lung tissue

Background. Tissue-resident macrophages can be educated to tumor-associated macrophages (TAMs) by the tumor microenvironment and many types of macrophages express erythropoietic receptor (EPOR); However, little is known about the expression of EPOR on TAMs and the identity of EPOR+ TAMs in osteosarcoma lung metastasis has thus far remained elusive. Methods. EPOR-eGFPcre mice were used to determine the expression of EPOR on lung tissue-resident macrophages. Flow cytometry, RT-PCR, and Western blot were examined to define the identity of EPOR+ TAMs in 106 osteosarcoma lung metastasis specimens. Moreover, the clinicopathologic factors and prognosis of patients with CD163+EPOR+ macrophages were compared. Results. We found that a subpopulation of mouse lung tissue-resident macrophages express EPOR and EPO enhances the proliferation of EPOR+ macrophages in mouse lung. A subpopulation of CD163+ macrophages expresses EPOR in human osteosarcoma lung metastasis specimens. CD163+EPOR+TAMs increase 2.5 times in human osteosarcoma lung metastasis tissues; CD206, CD163, and PD1, which are known to have a significant role in TAM function had high expression in CD163+EPOR+ TAMs compared with CD163+EPOR- TAMs. Furthermore, CD163+EPOR+ TAMs had higher M2 marker and cytokine expression in osteosarcoma tissues compared with para-osteosarcoma tissues. EPO enhanced the expression of M2 cytokines in primary CD163+EPOR+ TAMs. Importantly, the percentage of CD163+EPOR+ TAMs had a positive linear association with malignant phenotypes as well as poor disease-free survival and overall survival time. Conclusions. We have characterized TAMs expressing EPOR and CD163+EPOR+ macrophages as TAMs in osteosarcoma lung metastasis patients, which are highly associated with tumor aggressiveness.

Download Full-text

Mouse Lung Tissue Slice Culture

Methods in Molecular Biology - Mouse Cell Culture ◽

10.1007/978-1-4939-9086-3_21 ◽

2019 ◽

pp. 297-311 ◽

Cited By ~ 1

Author(s):

Xinhui Wu ◽

Eline M. van Dijk ◽

I. Sophie T. Bos ◽

Loes E. M. Kistemaker ◽

Reinoud Gosens

Keyword(s):

Lung Tissue ◽

Tissue Slice ◽

Mouse Lung ◽

Slice Culture ◽

Mouse Lung Tissue

Download Full-text

The effect of benzo[α]pyrene on expression and signaling cross talk of aryl hydrocarbon receptor and NFATc1 in mouse lung tissue

Toxicology and Industrial Health ◽

10.1177/0748233714555153 ◽

2014 ◽

Vol 32 (7) ◽

pp. 1246-1253 ◽

Cited By ~ 4

Author(s):

Maliheh Parsa ◽

Seyed Nasser Ostad ◽

Seyed Mohammad Hossein Noori Moogahi ◽

Mohammad Bayat ◽

Mohammad Hossein Ghahremani

Keyword(s):

Aryl Hydrocarbon Receptor ◽

Lung Tissue ◽

Cross Talk ◽

Environmental Pollutants ◽

Lung Damage ◽

Mouse Lung ◽

Aryl Hydrocarbon ◽

Embedded Blocks ◽

Mouse Lung Tissue ◽

Imagej Software

Objective: Polycyclic aromatic hydrocarbons (PAHs) are potent environmental pollutants. Benzo[α]pyrene (B[α]P) is the major compound of PAHs that acts by activating aryl hydrocarbon receptor (AhR) in cells. B[α]P is a known carcinogen and an immunotoxicant; however, its role with regard to nuclear factor of activated T cell (NFAT) pathway is unclear. AhR and NFAT signaling pathways have common roles in pathological functions in immunotoxicity and lung cancer. In this study, the effect of AhR activation on expression and signaling cross talk of AhR and NFATc1 pathways in mouse lung tissue has been investigated. Methods: Swiss albino mice were randomly allocated to five groups and administered with cyclosporin A (CsA) and B[α]P for seven constitutive days. Animals were then killed, and lung tissues were obtained after washing the whole blood. Paraffin-embedded blocks were prepared, and 5 µm sections were cut for histopathological and immunohistochemical assessments. The results were scored by observer and digitally analyzed using ImageJ software. Results: Our data showed that CsA administration resulted in a significant reduction of AhR expression. This effect was partly blocked in mice coadministrated with B[α]P and CsA. NFATc1 expression was also reduced in CsA-treated animals. Furthermore, CsA inhibited the pathological effects of B[α]P in mouse lung tissue. Conclusion: AhR expression is dependent on NFATc1 activation, and NFATc1 inhibition remarkably decreases AhR expression. However, it seems that total expression of NFATc1 is not dependent on AhR expression or activation. Moreover, CsA can prevent B[α]P-induced lung tissue damage, and it remarkably decreases NFATc1 expression. The results from this study point toward the molecular interactions of AhR and NFATc1 activation in lung tissue and the benefit of CsA treatment in B[α]P-induced lung damage.

Download Full-text

The effect of transplacental administration of ddt on organ cultures of foetal mouse lung tissue

International Journal of Cancer ◽

10.1002/ijc.2910090215 ◽

1972 ◽

Vol 9 (2) ◽

pp. 365-373 ◽

Cited By ~ 12

Author(s):

L. M. Shabad ◽

T. S. Kolesnichenko ◽

T. V. Nikonova

Keyword(s):

Lung Tissue ◽

Mouse Lung ◽

Organ Cultures ◽

Mouse Lung Tissue

Download Full-text

Transcriptional regulatory mechanisms of fibrosis development in mouse lung tissue exposed to carbon nanotubes

10.1101/363762 ◽

2018 ◽

Author(s):

Vadim Zhernovkov ◽

Tapesh Santra ◽

Hilary Cassidy ◽

Oleksii Rukhlenko ◽

David Matallanas ◽

...

Keyword(s):

Carbon Nanotubes ◽

Lung Tissue ◽

Stress Responses ◽

Expression Profiles ◽

Cellular Stress ◽

Interferon Response ◽

Mouse Lung ◽

M2 Macrophage ◽

Cellular Stress Responses ◽

Mouse Lung Tissue

AbstractBackgroundCarbon nanotubes (CNTs) usage has rapidly increased in the last few decades due to their unique properties, exploited in various industrial and commercial products. Certain types of CNTs cause adverse health effects, including chronic inflammation and fibrosis. Despite the large number of in vitro and in vivo studies evaluating these effects, many important questions remain unanswered due to a lack of mechanistic understanding of how CNTs induce cellular stress responses. In order to predict CNT toxicity, it is important to understand which transcriptional programs are specifically activated in response to CNTs, and what similarities and differences exist in relation to other toxic inducers exerting similar adverse effects.ResultsA systems biology approach was applied to reveal complex interactions at the molecular level in mouse lung tissue in response to different fibrosis inducers: two types of multi-walled CNTs, NM-401 and NRCWE-26, and bleomycin (BLM). Based on mRNA gene expression profiles, we inferred gene regulatory networks (GRNs) to capture functional hierarchical regulatory structures between genes and their regulators. We found that activities of the transcription factors (TFs) Myc, Arid5a and Mxd1 were associated with the regulation of cytokine transcription in response to CNTs, while in response to BLM treatment, Myc was associated with p53 signaling. TF Litaf was identified as the essential regulator for noncanonical signaling of TLR2/4 driven by CNTs. Despite the different nature of the lung injury caused by CNTs and BLM, we identified common stress response modules, that included DNA damage (TFs: E2f8, E2f1, Foxm1), M1/M2 macrophage polarization (TF: Mafb), Interferon response (TFs: Irf7, Stat2 and Irf9) for all agents.ConclusionsThese results suggest that the reconstruction and analysis of TF-centric gene interaction networks can reveal key targets and regulators of cellular stress responses to toxic agents.

Download Full-text

The activity of 7-methylbenz(a)anthracene metabolites in an in vitro-in vivo carcinogenicity test using mouse lung tissue

Cancer Letters ◽

10.1016/s0304-3835(77)95309-5 ◽

1977 ◽

Vol 3 ◽

pp. 163-167

Author(s):

Antonia Flaks ◽

Peter Sims

Keyword(s):

Lung Tissue ◽

Mouse Lung ◽

Mouse Lung Tissue

Download Full-text