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Article ; Online: Short-term exposure to cigarette smoke upregulates cathepsin S and alters expression of tight junction ZO-1.

Estur, Florent / Murigneux, Emilie / David, Alexis / Magnen, Mélia / Saidi, Ahlame / Lalmanach, Gilles / Lecaille, Fabien

Biochimie

2024

Abstract: A long-term exposure to cigarette smoke (CS) alters the integrity of airway epithelial barrier, contributes to lung dysfunction, and elicits the expression and activity of lung cathepsin S (CatS), a cysteine protease that participates in the remodeling ... ...

Abstract	A long-term exposure to cigarette smoke (CS) alters the integrity of airway epithelial barrier, contributes to lung dysfunction, and elicits the expression and activity of lung cathepsin S (CatS), a cysteine protease that participates in the remodeling of connective tissue and cell junctions. Here, we observed that a short-term (4 days) exposure of mice to CS increased the expression and activity of CatS, while the expression level of zonula occludens 1 (ZO-1), an epithelial tight junction protein that stabilizes barrier assembly, was reduced in lung tissue lysates. Present data support that proteolytically active CatS may contribute to the defect of ZO-1 in CS-exposed mice.
Language	English
Publishing date	2024-03-15
Publishing country	France
Document type	Journal Article
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2024.03.005
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Article: Optimizing anesthesia and delivery approaches for dosing into lungs of mice.

Seo, Yurim / Qiu, Longhui / Magnen, Mélia / Conrad, Catharina / Moussavi-Harami, S Farshid / Looney, Mark R / Cleary, Simon J

bioRxiv : the preprint server for biology

2023

Abstract: Microbes, toxins, therapeutics and cells are often instilled into lungs of mice to model diseases and test experimental interventions. Consistent pulmonary delivery is critical for experimental power and reproducibility, but we observed variation in ... ...

Abstract	Microbes, toxins, therapeutics and cells are often instilled into lungs of mice to model diseases and test experimental interventions. Consistent pulmonary delivery is critical for experimental power and reproducibility, but we observed variation in outcomes between handlers using different anesthetic approaches for intranasal dosing into mice. We therefore used a radiotracer to quantify lung delivery after intranasal dosing under inhalational (isoflurane) versus injectable (ketamine/xylazine) anesthesia in C57BL/6 mice. We found that ketamine/xylazine anesthesia resulted in delivery of a greater proportion (52±9%) of an intranasal dose to lungs relative to isoflurane anesthesia (30±15%). This difference in pulmonary dose delivery altered key outcomes in models of viral and bacterial pneumonia, with mice anesthetized with ketamine/xylazine for intranasal infection with influenza A virus or Pseudomonas aeruginosa developing more robust lung inflammation responses relative to control animals randomized to isoflurane anesthesia. Pulmonary dosing efficiency through oropharyngeal aspiration was not affected by anesthetic method and resulted in delivery of 63±8% of dose to lungs, and a non-surgical intratracheal dosing approach further increased lung delivery to 92±6% of dose. Use of either of these more precise dosing methods yielded greater experimental power in the bacterial pneumonia model relative to intranasal infection. Both anesthetic approach and dosing route can impact pulmonary dosing efficiency. These factors affect experimental power and so should be considered when planning and reporting studies involving delivery of fluids to lungs of mice.
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.01.526706
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Article ; Online: Optimizing anesthesia and delivery approaches for dosing into lungs of mice.

Seo, Yurim / Qiu, Longhui / Magnen, Mélia / Conrad, Catharina / Moussavi-Harami, S Farshid / Looney, Mark R / Cleary, Simon J

American journal of physiology. Lung cellular and molecular physiology

2023 Volume 325, Issue 2, Page(s) L262–L269

Abstract: Microbes, toxins, therapeutics, and cells are often instilled into lungs of mice to model diseases and test experimental interventions. Consistent pulmonary delivery is critical for experimental power and reproducibility, but we observed variation in ... ...

Abstract	Microbes, toxins, therapeutics, and cells are often instilled into lungs of mice to model diseases and test experimental interventions. Consistent pulmonary delivery is critical for experimental power and reproducibility, but we observed variation in outcomes between handlers using different anesthetic approaches for intranasal dosing in mice. We therefore used a radiotracer to quantify lung delivery after intranasal dosing under inhalational (isoflurane) versus injectable (ketamine/xylazine) anesthesia in C57BL/6 mice. We found that ketamine/xylazine anesthesia resulted in delivery of a greater proportion (52 ± 9%) of an intranasal dose to lungs relative to isoflurane anesthesia (30 ± 15%). This difference in pulmonary dose delivery altered key outcomes in models of viral and bacterial pneumonia, with mice anesthetized with ketamine/xylazine for intranasal infection with influenza A virus or
MeSH term(s)	Animals ; Mice ; Anesthesia/methods ; Anesthetics ; Isoflurane ; Ketamine ; Lung ; Mice, Inbred C57BL ; Reproducibility of Results ; Xylazine
Chemical Substances	Anesthetics ; Isoflurane (CYS9AKD70P) ; Ketamine (690G0D6V8H) ; Xylazine (2KFG9TP5V8)
Language	English
Publishing date	2023-07-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00046.2023
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Article ; Online: Update on animal models for COVID-19 research.

Cleary, Simon J / Magnen, Mélia / Looney, Mark R / Page, Clive P

British journal of pharmacology

2020 Volume 177, Issue 24, Page(s) 5679–5681

MeSH term(s)	Angiotensin-Converting Enzyme 2/metabolism ; Animals ; COVID-19/transmission ; Disease Models, Animal ; Masks ; Mesocricetus ; Mice ; SARS-CoV-2
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-11-02
Publishing country	England
Document type	Letter
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15266
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Article: Decoding functional hematopoietic progenitor cells in the adult human lung.

Conrad, Catharina / Magnen, Melia / Tsui, Jessica / Wismer, Harrison / Naser, Mohammad / Venkataramani, Urmila / Samad, Bushra / Cleary, Simon J / Qiu, Longhui / Tian, Jennifer J / De Giovanni, Marco / Mende, Nicole / Passegue, Emmanuelle / Laurenti, Elisa / Combes, Alexis J / Looney, Mark R

Research square

2024

Abstract: The bone marrow is the main site of blood cell production in adults, however, rare pools of hematopoietic stem and progenitor cells with self-renewal and differentiation potential have been found in extramedullary organs. The lung is primarily known for ... ...

Abstract	The bone marrow is the main site of blood cell production in adults, however, rare pools of hematopoietic stem and progenitor cells with self-renewal and differentiation potential have been found in extramedullary organs. The lung is primarily known for its role in gas exchange but has recently been described as a site of blood production in mice. Here, we show that functional hematopoietic precursors reside in the extravascular spaces of the human lung, at a frequency similar to the bone marrow, and are capable of proliferation and engraftment. The organ-specific gene signature of pulmonary and medullary CD34
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3576483/v2
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Article: Biophysical Changes of Leukocyte Activation (and NETosis) in the Cellular Host Response to Sepsis.

Sorrells, Matt G / Seo, Yurim / Magnen, Melia / Broussard, Bliss / Sheybani, Roya / Shah, Ajay M / O'Neal, Hollis R / Tse, Henry T K / Looney, Mark R / Di Carlo, Dino

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 8

Abstract: Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this ... ...

Abstract	Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a cohort of subjects was segregated into Control and Diseased populations and tested for levels of NET components (citrullinated histone (cit-H3) DNA and neutrophil elastase (NE) DNA) using customized ELISA assays and correlated with ISI scores from the same patient samples. Significant increases in IntelliSep Index (ISI) scores were observed with increasing concentrations of PMA in healthy blood (0 and 200:
Language	English
Publishing date	2023-04-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13081435
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Article: Update on animal models for COVID-19 research

Cleary, Simon J / Magnen, Mélia / Looney, Mark R / Page, Clive P

Br. j. pharmacol

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #900978
Database	COVID19

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Article ; Online: Kallikrein-related peptidases in lung diseases.

Lenga Ma Bonda, Woodys / Iochmann, Sophie / Magnen, Mélia / Courty, Yves / Reverdiau, Pascale

Biological chemistry

2018 Volume 399, Issue 9, Page(s) 959–971

Abstract: Human tissue kallikreins (KLKs) are 15 members of the serine protease family and are present in various healthy human tissues including airway tissues. Multiple studies have revealed their crucial role in the pathophysiology of a number of chronic, ... ...

Abstract	Human tissue kallikreins (KLKs) are 15 members of the serine protease family and are present in various healthy human tissues including airway tissues. Multiple studies have revealed their crucial role in the pathophysiology of a number of chronic, infectious and tumour lung diseases. KLK1, 3 and 14 are involved in asthma pathogenesis, and KLK1 could be also associated with the exacerbation of this inflammatory disease caused by rhinovirus. KLK5 was demonstrated as an influenza virus activating protease in humans, and KLK1 and 12 could also be involved in the activation and spread of these viruses. KLKs are associated with lung cancer, with up- or downregulation of expression depending on the KLK, cancer subtype, stage of tumour and also the microenvironment. Functional studies showed that KLK12 is a potent pro-angiogenic factor. Moreover, KLK6 promotes malignant-cell proliferation and KLK13 invasiveness. In contrast, KLK8 and KLK10 reduce proliferation and invasion of malignant cells. Considering the involvement of KLKs in various physiological and pathological processes, KLKs appear to be potential biomarkers and therapeutic targets for lung diseases.
MeSH term(s)	Cell Proliferation ; Humans ; Kallikreins/metabolism ; Lung Diseases/enzymology ; Lung Diseases/pathology ; Lung Neoplasms/enzymology ; Lung Neoplasms/pathology
Chemical Substances	Kallikreins (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2018-06-01
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1334659-3
ISSN	1437-4315 ; 1431-6730 ; 1432-0355
ISSN (online)	1437-4315
ISSN	1431-6730 ; 1432-0355
DOI	10.1515/hsz-2018-0114
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Article ; Online: Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression.

Valet, Colin / Magnen, Mélia / Qiu, Longhui / Cleary, Simon J / Wang, Kristin M / Ranucci, Serena / Grockowiak, Elodie / Boudra, Rafik / Conrad, Catharina / Seo, Yurim / Calabrese, Daniel R / Greenland, John R / Leavitt, Andrew D / Passegué, Emmanuelle / Méndez-Ferrer, Simón / Swirski, Filip K / Looney, Mark R

The Journal of clinical investigation

2022 Volume 132, Issue 7

Abstract: Platelets have a wide range of functions including critical roles in hemostasis, thrombosis, and immunity. We hypothesized that during acute inflammation, such as in life-threatening sepsis, there are fundamental changes in the sites of platelet ... ...

Abstract	Platelets have a wide range of functions including critical roles in hemostasis, thrombosis, and immunity. We hypothesized that during acute inflammation, such as in life-threatening sepsis, there are fundamental changes in the sites of platelet production and phenotypes of resultant platelets. Here, we showed during sepsis that the spleen was a major site of megakaryopoiesis and platelet production. Sepsis provoked an adrenergic-dependent mobilization of megakaryocyte-erythrocyte progenitors (MEPs) from the bone marrow to the spleen, where IL-3 induced their differentiation into megakaryocytes (MKs). In the spleen, immune-skewed MKs produced a CD40 ligandhi platelet population with potent immunomodulatory functions. Transfusions of post-sepsis platelets enriched from splenic production enhanced immune responses and reduced overall mortality in sepsis-challenged animals. These findings identify a spleen-derived protective platelet population that may be broadly immunomodulatory in acute inflammatory states such as sepsis.
MeSH term(s)	Animals ; Blood Platelets/metabolism ; CD40 Ligand ; Megakaryocytes ; Sepsis/metabolism ; Spleen
Chemical Substances	CD40 Ligand (147205-72-9)
Language	English
Publishing date	2022-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI153920
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Article ; Online: Kallikrein-related peptidase 5 and seasonal influenza viruses, limitations of the experimental models for activating proteases.

Magnen, Mélia / Elsässer, Brigitta Margit / Zbodakova, Olga / Kasparek, Petr / Gueugnon, Fabien / Petit-Courty, Agnès / Sedlacek, Radislav / Goettig, Peter / Courty, Yves

Biological chemistry

2018 Volume 399, Issue 9, Page(s) 1053–1064

Abstract: Every year, influenza A virus (IAV) affects and kills many people worldwide. The viral hemagglutinin (HA) is a critical actor in influenza virus infectivity which needs to be cleaved by host serine proteases to exert its activity. KLK5 has been ... ...

Abstract	Every year, influenza A virus (IAV) affects and kills many people worldwide. The viral hemagglutinin (HA) is a critical actor in influenza virus infectivity which needs to be cleaved by host serine proteases to exert its activity. KLK5 has been identified as an activating protease in humans with a preference for the H3N2 IAV subtype. We investigated the origin of this preference using influenza A/Puerto Rico/8/34 (PR8, H1N1) and A/Scotland/20/74 (Scotland, H3N2) viruses. Pretreatment of noninfectious virions with human KLK5 increased infectivity of Scotland IAV in MDCK cells and triggered influenza pneumonia in mice. These effects were not observed with the PR8 IAV. Molecular modeling and in vitro enzymatic studies of peptide substrates and recombinant HAs revealed that the sequences around the cleavage site do not represent the sole determinant of the KLK5 preference for the H3N2 subtype. Using mouse Klk5 and Klk5-deficient mice, we demonstrated in vitro and in vivo that the mouse ortholog protease is not an IAV activating enzyme. This may be explained by unfavorable interactions between H3 HA and mKlk5. Our data highlight the limitations of some approaches used to identify IAV-activating proteases.
MeSH term(s)	Animals ; Disease Models, Animal ; Dogs ; Humans ; Influenza A virus/metabolism ; Kallikreins/deficiency ; Kallikreins/metabolism ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Knockout ; Models, Molecular ; Seasons ; Serine Proteases/metabolism
Chemical Substances	Serine Proteases (EC 3.4.-) ; KLK5 protein, human (EC 3.4.21.-) ; Kallikreins (EC 3.4.21.-)
Language	English
Publishing date	2018-06-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1334659-3
ISSN	1437-4315 ; 1431-6730 ; 1432-0355
ISSN (online)	1437-4315
ISSN	1431-6730 ; 1432-0355
DOI	10.1515/hsz-2017-0340
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