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Article ; Online: Identification and Characterization of Alveolar and Recruited Lung Macrophages during Acute Lung Inflammation.

Han, Wei / Tanjore, Harikrishna / Liu, Yang / Hunt, Raphael P / Gutor, Sergey S / Serezani, Ana P M / Blackwell, Timothy S

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 210, Issue 11, Page(s) 1827–1836

Abstract: To precisely identify mouse resident alveolar macrophages (AMs) and bone marrow (BM)-derived macrophages, we developed a technique to separately label AMs and BM-derived macrophages with a fluorescent lipophilic dye followed by FACS. We showed that this ... ...

Abstract	To precisely identify mouse resident alveolar macrophages (AMs) and bone marrow (BM)-derived macrophages, we developed a technique to separately label AMs and BM-derived macrophages with a fluorescent lipophilic dye followed by FACS. We showed that this technique overcomes issues in cell identification related to dynamic shifts in cell surface markers that occurs during lung inflammation. We then used this approach to track macrophage subsets at different time points after intratracheal (i.t.) instillation of Escherichia coli LPS. By isolating BM-derived macrophages and AMs, we demonstrated that BM-derived macrophages were enriched in expression of genes in signal transduction and immune system activation pathways whereas resident AMs were enriched in cellular processes, such as lysosome/phagosome pathways, efferocytosis, and metabolic pathways related to fatty acids and peroxisomes. Taken together, these data indicate that more accurate identification of macrophage origin can result in improved understanding of differential phenotypes and functions between AMs and BM-derived macrophages in the lungs.
MeSH term(s)	Mice ; Animals ; Macrophages, Alveolar ; Lung ; Pneumonia/metabolism ; Macrophages/metabolism
Language	English
Publishing date	2023-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200694
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Article ; Online: Endoplasmic reticulum stress in pulmonary fibrosis.

Burman, Ankita / Tanjore, Harikrishna / Blackwell, Timothy S

Matrix biology : journal of the International Society for Matrix Biology

2018 Volume 68-69, Page(s) 355–365

Abstract: Endoplasmic reticulum (ER) stress is associated with development and progression of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). ER stress was first implicated in the pathogenesis of IPF >15 years ago with the discovery of disease- ... ...

Abstract	Endoplasmic reticulum (ER) stress is associated with development and progression of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). ER stress was first implicated in the pathogenesis of IPF >15 years ago with the discovery of disease-causing mutations in surfactant protein C, which result in a misfolded gene product in type II alveolar epithelial cells (AECs). ER stress and the unfolded protein response (UPR) have been linked to lung fibrosis through regulation of AEC apoptosis, epithelial-mesenchymal transition, myofibroblast differentiation, and M2 macrophage polarization. Although progress has been made in understanding the causes and consequences of ER stress in IPF and a number of chronic fibrotic disorders, further studies are needed to identify key factors that induce ER stress in important cell types and define critical down-stream processes and effector molecules that mediate ER stress-related phenotypes. This review discusses potential causes of ER stress induction in the lungs and current evidence linking ER stress to fibrosis in the context of individual cell types: AECs, fibroblasts, and macrophages. As our understanding of the relationship between ER stress and lung fibrosis continues to evolve, future studies will examine new strategies to modulate UPR pathways for therapeutic benefit.
MeSH term(s)	Alveolar Epithelial Cells/metabolism ; Animals ; Cell Polarity ; Disease Progression ; Endoplasmic Reticulum Stress ; Epithelial-Mesenchymal Transition ; Humans ; Pulmonary Fibrosis/metabolism ; Unfolded Protein Response
Language	English
Publishing date	2018-03-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1183793-7
ISSN	1569-1802 ; 0945-053X
ISSN (online)	1569-1802
ISSN	0945-053X
DOI	10.1016/j.matbio.2018.03.015
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Zs.A 1694: Show issues

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Article ; Online: KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models.

West, James D / Austin, Eric D / Rizzi, Elise M / Yan, Ling / Tanjore, Harikrishna / Crabtree, Amber L / Moore, Christy S / Muthian, Gladson / Carrier, Erica J / Jacobson, David A / Hamid, Rizwan / Kendall, Peggy L / Majka, Susan / Rathinasabapathy, Anandharajan

International journal of molecular sciences

2021 Volume 22, Issue 9

Abstract: Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple ... ...

Abstract	Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we exposed
MeSH term(s)	Animals ; Biomarkers ; Case-Control Studies ; Cytokines/metabolism ; Disease Models, Animal ; Disease Susceptibility ; Gene Expression Profiling ; Genetic Predisposition to Disease ; Humans ; Hypoxia/genetics ; Hypoxia/metabolism ; Immunomodulation/genetics ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Mice ; Mice, Knockout ; Models, Biological ; Monocytes/immunology ; Monocytes/metabolism ; Mutation ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Potassium Channels, Tandem Pore Domain/genetics ; Potassium Channels, Tandem Pore Domain/metabolism ; Pulmonary Arterial Hypertension/complications ; Pulmonary Arterial Hypertension/genetics ; Pulmonary Arterial Hypertension/immunology ; Pulmonary Arterial Hypertension/physiopathology ; Transcriptome
Chemical Substances	Biomarkers ; Cytokines ; Nerve Tissue Proteins ; Potassium Channels, Tandem Pore Domain ; potassium channel subfamily K member 3 (1HQ3YCN4GS)
Language	English
Publishing date	2021-05-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22095014
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Article ; Online: Multiplatform Single-Cell Analysis Identifies Immune Cell Types Enhanced in Pulmonary Fibrosis.

Serezani, Ana P M / Pascoalino, Bruno D / Bazzano, Julia M R / Vowell, Katherine N / Tanjore, Harikrishna / Taylor, Chase J / Calvi, Carla L / McCall, A Scott / Bacchetta, Matthew D / Shaver, Ciara M / Ware, Lorraine B / Salisbury, Margaret L / Banovich, Nicholas E / Kendall, Peggy L / Kropski, Jonathan A / Blackwell, Timothy S

American journal of respiratory cell and molecular biology

2022 Volume 67, Issue 1, Page(s) 50–60

Abstract: Immune cells have been implicated in idiopathic pulmonary fibrosis (IPF), but the phenotypes and effector mechanisms of these cells remain incompletely characterized. We performed mass cytometry to quantify immune cell subsets in lungs of 12 patients ... ...

Abstract	Immune cells have been implicated in idiopathic pulmonary fibrosis (IPF), but the phenotypes and effector mechanisms of these cells remain incompletely characterized. We performed mass cytometry to quantify immune cell subsets in lungs of 12 patients with IPF and 15 organ donors without chronic lung disease and used existing single-cell RNA-sequencing data to investigate transcriptional profiles of immune cells overrepresented in IPF. Among myeloid cells, we found increased numbers of alveolar macrophages (AMØs) and dendritic cells (DCs) in IPF, as well as a subset of monocyte-derived DCs. In contrast, monocyte-like cells and interstitial macrophages were reduced in IPF. Transcriptomic profiling identified an enrichment for IFN-γ response pathways in AMØs and DCs from IPF, as well as antigen processing in DCs and phagocytosis in AMØs. Among T cells, we identified three subsets of memory T cells that were increased in IPF, including CD4
MeSH term(s)	Gene Expression Profiling ; Humans ; Idiopathic Pulmonary Fibrosis/pathology ; Lung/pathology ; Macrophages, Alveolar/metabolism ; Single-Cell Analysis
Language	English
Publishing date	2022-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1025960-0
ISSN	1535-4989 ; 1044-1549
ISSN (online)	1535-4989
ISSN	1044-1549
DOI	10.1165/rcmb.2021-0418OC
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Zs.A 2851: Show issues

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Article ; Online: Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis.

Tanjore, Harikrishna / Blackwell, Timothy S / Lawson, William E

American journal of physiology. Lung cellular and molecular physiology

2012 Volume 302, Issue 8, Page(s) L721–9

Abstract: While the factors that regulate the onset and progression of idiopathic pulmonary fibrosis (IPF) are incompletely understood, recent investigations have revealed that endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) ...

Abstract	While the factors that regulate the onset and progression of idiopathic pulmonary fibrosis (IPF) are incompletely understood, recent investigations have revealed that endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are prominent in alveolar epithelial cells in this disease. Initial observations linking ER stress and IPF were made in cases of familial interstitial pneumonia (FIP), the familial form of IPF, in a family with a mutation in surfactant protein C (SFTPC). Subsequent studies involving lung biopsy specimens revealed that ER stress markers are highly expressed in the alveolar epithelium in IPF and FIP. Recent mouse modeling has revealed that induction of ER stress in the alveolar epithelium predisposed to enhanced lung fibrosis after treatment with bleomycin, which is mediated at least in part by increased alveolar epithelial cell (AEC) apoptosis. Emerging data also indicate that ER stress in AECs could impact fibrotic remodeling by altering inflammatory responses and inducing epithelial-mesenchymal transition. Although the cause of ER stress in IPF remains unknown, common environmental exposures such as herpesviruses, inhaled particulates, and cigarette smoke induce ER stress and are candidates for contributing to AEC dysfunction by this mechanism. Together, investigations to date suggest that ER stress predisposes to AEC dysfunction and subsequent lung fibrosis. However, many questions remain regarding the role of ER stress in initiation and progression of lung fibrosis, including whether ER stress or the UPR could be targeted for therapeutic benefit.
MeSH term(s)	Aging ; Animals ; Apoptosis/drug effects ; Bleomycin/adverse effects ; Endoplasmic Reticulum Stress/drug effects ; Endoplasmic Reticulum Stress/physiology ; Epithelial-Mesenchymal Transition/drug effects ; Humans ; Idiopathic Pulmonary Fibrosis/chemically induced ; Idiopathic Pulmonary Fibrosis/etiology ; Idiopathic Pulmonary Fibrosis/pathology ; Inflammation/etiology ; Inflammation/pathology ; Mice ; Pulmonary Alveoli/drug effects ; Pulmonary Alveoli/metabolism ; Pulmonary Surfactant-Associated Protein C/genetics ; Pulmonary Surfactant-Associated Protein C/metabolism ; Smoking/adverse effects ; Unfolded Protein Response/drug effects ; Unfolded Protein Response/physiology
Chemical Substances	Pulmonary Surfactant-Associated Protein C ; Bleomycin (11056-06-7)
Language	English
Publishing date	2012-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00410.2011
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Zs.A 2749: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)

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Article: Endoplasmic reticulum stress as a pro-fibrotic stimulus.

Tanjore, Harikrishna / Lawson, William E / Blackwell, Timothy S

Biochimica et biophysica acta

2012 Volume 1832, Issue 7, Page(s) 940–947

Abstract: Current evidence suggests a prominent role for endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in fibrotic conditions affecting a number of internal organs, including the lungs, liver, GI tract, kidney, and heart. ... ...

Abstract	Current evidence suggests a prominent role for endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in fibrotic conditions affecting a number of internal organs, including the lungs, liver, GI tract, kidney, and heart. ER stress enhances the susceptibility of structural cells, in most cases the epithelium, to pro-fibrotic stimuli. Studies suggest that ER stress facilitates fibrotic remodeling through activation of pro-apoptotic pathways, induction of epithelial-mesenchymal transition, and promotion of inflammatory responses. While genetic mutations that lead to ER stress underlie some cases of fibrosis, including lung fibrosis secondary to mutations in surfactant protein C (SFTPC), a variety of other factors can cause ER stress. These ER stress inducing factors include metabolic abnormalities, oxidative stress, viruses, and environmental exposures. Interestingly, the ability of the ER to maintain homeostasis under stress diminishes with age, potentially contributing to the fact that fibrotic disorders increase in incidence with aging. Taken together, underlying ER stress and UPR pathways are emerging as important determinants of fibrotic remodeling in different forms of tissue fibrosis. Further work is needed to better define the mechanisms by which ER stress facilitates progressive tissue fibrosis. In addition, it remains to be seen whether targeting ER stress and the UPR could have therapeutic benefit. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.
MeSH term(s)	Animals ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress ; Epithelial-Mesenchymal Transition ; Humans ; Lung/metabolism ; Oxidative Stress ; Pulmonary Fibrosis ; Unfolded Protein Response
Language	English
Publishing date	2012-11-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2012.11.011
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Article: The role of type IV collagen and basement membranes in cancer progression and metastasis.

Tanjore, Harikrishna / Kalluri, Raghu

The American journal of pathology

2006 Volume 168, Issue 3, Page(s) 715–717

MeSH term(s)	Basement Membrane/chemistry ; Basement Membrane/metabolism ; Collagen Type IV/genetics ; Collagen Type IV/metabolism ; Collagen Type IV/physiology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; DNA Methylation ; Disease Progression ; Gene Expression ; Humans ; Neoplasm Metastasis
Chemical Substances	Collagen Type IV
Language	English
Publishing date	2006-03
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.2353/ajpath.2006.051321
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Article ; Online: Ligand-independent integrin β1 signaling supports lung adenocarcinoma development.

JCI insight

2022 Volume 7, Issue 15

Abstract: Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted ... ...

Abstract	Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that the highly expressed integrin β1 subunit is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin β1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin β1-mediated adhesion to ECM but are dependent on integrin β1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). These studies support a critical role for integrin β1 in lung tumorigenesis that is mediated through constitutive, ECM binding-independent signaling involving the cytoplasmic tail.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma of Lung/genetics ; Animals ; Humans ; Integrin beta1/genetics ; Integrin beta1/metabolism ; Integrins ; Ligands ; Lung Neoplasms/pathology ; Mice
Chemical Substances	Integrin beta1 ; Integrins ; Ligands
Language	English
Publishing date	2022-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.154098
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Article ; Online: Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.

American journal of respiratory and critical care medicine

2022 Volume 206, Issue 5, Page(s) 596–607

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Animals ; Bleomycin/pharmacology ; F2-Isoprostanes/metabolism ; Fibroblasts/metabolism ; Humans ; Idiopathic Pulmonary Fibrosis/genetics ; Lung/metabolism ; Mice ; Mice, Inbred C57BL ; Prostaglandins/metabolism ; Receptors, Thromboxane/metabolism ; Thromboxanes/metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	F2-Isoprostanes ; Prostaglandins ; Receptors, Thromboxane ; Thromboxanes ; Transforming Growth Factor beta ; Bleomycin (11056-06-7)
Language	English
Publishing date	2022-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202106-1503OC
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Article ; Online: Localized hypoxia links ER stress to lung fibrosis through induction of C/EBP homologous protein.

Burman, Ankita / Kropski, Jonathan A / Calvi, Carla L / Serezani, Ana P / Pascoalino, Bruno D / Han, Wei / Sherrill, Taylor / Gleaves, Linda / Lawson, William E / Young, Lisa R / Blackwell, Timothy S / Tanjore, Harikrishna

JCI insight

2018 Volume 3, Issue 16

Abstract: ER stress in type II alveolar epithelial cells (AECs) is common in idiopathic pulmonary fibrosis (IPF), but the contribution of ER stress to lung fibrosis is poorly understood. We found that mice deficient in C/EBP homologous protein (CHOP), an ER stress- ...

Abstract	ER stress in type II alveolar epithelial cells (AECs) is common in idiopathic pulmonary fibrosis (IPF), but the contribution of ER stress to lung fibrosis is poorly understood. We found that mice deficient in C/EBP homologous protein (CHOP), an ER stress-regulated transcription factor, were protected from lung fibrosis and AEC apoptosis in 3 separate models where substantial ER stress was identified. In mice treated with repetitive intratracheal bleomycin, we identified localized hypoxia in type II AECs as a potential mechanism explaining ER stress. To test the role of hypoxia in lung fibrosis, we treated mice with bleomycin, followed by exposure to 14% O2, which exacerbated ER stress and lung fibrosis. Under these experimental conditions, CHOP-/- mice, but not mice with epithelial HIF (HIF1/HIF2) deletion, were protected from AEC apoptosis and fibrosis. In vitro studies revealed that CHOP regulates hypoxia-induced apoptosis in AECs via the inositol-requiring enzyme 1α (IRE1α) and the PKR-like ER kinase (PERK) pathways. In human IPF lungs, CHOP and hypoxia markers were both upregulated in type II AECs, supporting a conclusion that localized hypoxia results in ER stress-induced CHOP expression, thereby augmenting type II AEC apoptosis and potentiating lung fibrosis.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Bleomycin/toxicity ; Cell Hypoxia/drug effects ; Cells, Cultured ; Disease Models, Animal ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum/pathology ; Endoplasmic Reticulum Stress ; Endoribonucleases/metabolism ; Female ; Humans ; Idiopathic Pulmonary Fibrosis/chemically induced ; Idiopathic Pulmonary Fibrosis/pathology ; Male ; Mice ; Mice, Knockout ; Protein Serine-Threonine Kinases/metabolism ; Pulmonary Alveoli/drug effects ; Pulmonary Alveoli/metabolism ; Pulmonary Alveoli/pathology ; Transcription Factor CHOP/genetics ; Transcription Factor CHOP/metabolism ; eIF-2 Kinase/metabolism
Chemical Substances	DDIT3 protein, human ; Ddit3 protein, mouse ; Bleomycin (11056-06-7) ; Transcription Factor CHOP (147336-12-7) ; Ern1 protein, mouse (EC 2.7.11.1) ; PERK kinase (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; eIF-2 Kinase (EC 2.7.11.1) ; Endoribonucleases (EC 3.1.-)
Language	English
Publishing date	2018-08-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.99543
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