Review
Immunology
Lars Hellman, Srinivas Akula, Zhirong Fu, Sara Wernersson
Summary: Proteases stored in mast cells have multiple functions, including maintaining connective tissue homeostasis, regulating blood pressure, and exhibiting anticoagulant activity. They can also modulate immune responses and provide protection against ectoparasites.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Srinivas Akula, Zhirong Fu, Sara Wernersson, Lars Hellman
Summary: The chymase locus in mammals encodes multiple protease genes and has undergone expansions during evolution, with different species showing variations in gene numbers and specificities which may affect immune functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Rahel Dani, Gabor Oroszlan, Robert Martinusz, Bence Farkas, Bernadett Dobos, Evelin Vadas, Peter Zavodszky, Peter Gal, Jozsef Dobo
Summary: Complement factor D (FD) is a self-inhibited protease that is continuously converted from pro-FD by circulating active MASP-3. FD has low activity towards free FB but is highly efficient towards C3bB. The cleavage rate of FB is enhanced 20 million-fold when it forms a complex with C3b.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Zhadyra Mustafa, Anuar Zhanapiya, Hubert Kalbacher, Timo Burster
Summary: Serine proteases released by activated neutrophils play important roles in immune responses and can be hijacked by viruses to evade immune detection. NE and PR3, but not CatG, hydrolyze the scissile peptide bond adjacent to the polybasic amino acid sequence of S1/S2 interface in SARS-CoV-2, suggesting their involvement in priming the virus during an immune response.
Review
Biochemistry & Molecular Biology
Shamila Vibhushan, Manuela Bratti, Juan Eduardo Montero-Hernandez, Alaa El Ghoneimi, Marc Benhamou, Nicolas Charles, Eric Daugas, Ulrich Blank
Summary: Chymase, an important protease found in mast cells, plays a key role in the development of kidney disease, contributing to the generation of angiotensin II, an important inflammatory mediator. While initially thought to contribute to pathogenesis, accumulating data suggest that chymase may also have beneficial effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Allergy
Xinran O. Zhao, Maria Lampinen, Ola Rollman, Christian P. Sommerhoff, Aida Paivandy, Gunnar Pejler
Summary: MC proteases can influence the functionality of human lung fibroblasts, with chymase having a major impact on cellular morphology, extracellular matrix composition, and proinflammatory phenotype.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Elin Ronnberg, Avinash Ravindran, Luca Mazzurana, Yitao Gong, Jesper Safholm, Julie Lorent, Olga Dethlefsen, Ann-Charlotte Orre, Mamdoh Al-Ameri, Mikael Adner, Sven-Erik Dahlen, Joakim S. Dahlin, Jenny Mjosberg, Gunnar Nilsson
Summary: Mast cells are important in maintaining normal bodily functions and are involved in lung inflammatory diseases such as asthma. Human lung mast cells are divided into two subsets, MCT and MCTC, based on their protein expression. However, very little is known about the heterogeneity of these cells. In this study, single cell RNA sequencing was performed to analyze the gene expression profiles of sorted human lung mast cells. The results showed high expression of classical mast cell markers, and significant variation in the expression of individual genes. Although no distinct subpopulations were identified, certain protease-encoding genes showed different levels of expression. The findings suggest that human lung mast cells are primarily of the MCT subset, and the expression of certain genes is not always consistent with protein expression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Sabrina Sofia Burgener, Melanie Brugger, Nathan Georges Francois Leborgne, Sophia Sollberger, Paola Basilico, Thomas Kaufmann, Phillip Ian Bird, Charaf Benarafa
Summary: Mast cells are immune cells that release serine proteases which modulate physiological functions and induce mast cell death. The pathways involved in granule-mediated mast cell apoptosis are regulated by a balance of serpin protease inhibitors, with granzyme B playing a critical role in mast cell survival.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Microbiology
Yu-Na Wang, Yun-Fa Zhang, Xue-Fang Peng, Hong-Han Ge, Gang Wang, Heng Ding, Yue Li, Shuang Li, Ling-Yu Zhang, Jing-Tao Zhang, Hao Li, Xiao-Ai Zhang, Wei Liu
Summary: This study reveals the pathogenic role of mast cells (MCs) in response to severe fever with thrombocytopenia syndrome virus (SFTSV) infection. It also identifies potential biomarkers to differentiate SFTS patients with fatal outcomes and suggests novel therapeutic targets for the clinical management of SFTS. These findings shed light on the potential of MCs as a drug target in other viral hemorrhagic fever diseases with similar host pathology as SFTS.
MICROBIOLOGY SPECTRUM
(2022)
Article
Allergy
Xinran O. Zhao, Christian P. Sommerhoff, Aida Paivandy, Gunnar Pejler
Summary: Mast cell proteases, specifically chymase, have extensive effects on airway epithelial cells, particularly in processes related to extracellular matrix (ECM) remodeling. Chymase suppresses ECM-related genes, degrades fibronectin, suppresses the migratory capacity of airway epithelial cells, and degrades the cell-cell contact protein E-cadherin. These findings suggest the involvement of chymase in the regulation of ECM remodeling events mediated by airway epithelial cells.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Xixi Lu, Jie Liu, Tao Wei, Xiaoying Zhou
Summary: This study revealed that MC-chymase promotes bradykinin production to stimulate GFs and maintain the continuous inflammation process in gingival tissues of CP patients. Bradykinin affects gingival inflammation by promoting GF proliferation, matrix metalloproteinase activity, and activation of intracellular signaling pathways.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Microbiology
Lucas Vellasco, Erik Svensjo, Carlos Alberto Bulant, Pablo Javier Blanco, Fabio Nogueira, Gilberto Domont, Natalia Pinto de Almeida, Clarissa Rodrigues Nascimento, Danielle Silva-dos-Santos, Carla Eponina Carvalho-Pinto, Emiliano Horacio Medei, Igor C. Almeida, Julio Scharfstein
Summary: Microangiopathy may worsen the clinical outcome of Chagas disease. This study used intravital microscopy to investigate microcirculatory alterations in the hamster cheek pouch infected by GFP-expressing T. cruzi. The findings suggest that intracellular amastigotes stimulate angiogenesis and enhance the delivery of plasma-borne nutrients and factors, benefiting the host-parasite relationship.
Article
Surgery
Lauren Hansen, Helen D. Brasch, Erin Paterson, Josie Patel, Nicholas Bockett, Paul F. Davis, Swee T. Tan
Summary: This study demonstrated the expression of cathepsins B, D, and G in AVM, with cathepsins B and D expressed by the primitive population and cathepsin G localized to mast cells within the AVM nidus.
FRONTIERS IN SURGERY
(2021)
Article
Biochemical Research Methods
Ahlame Saidi, Mylene Wartenberg, Jean-Baptiste Madinier, Guy Ilango, Seda Seren, Brice Korkmaz, Fabien Lecaille, Vincent Aucagne, Gilles Lalmanach
Summary: The near-infrared fluorescent substrate-based probe (pro3-SBP) is a convenient tool for monitoring hPR3 activity, showing high specificity and sensitivity in detecting human neutrophil activation processes. It can be successfully hydrolyzed by activated human neutrophils and provides a strong signal under confocal microscopy.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biotechnology & Applied Microbiology
Zhiqiang Li, Cejuan Ji, Jinzhi Cheng, Magnus Abrink, Tao Shen, Xiaoyuan Kuang, Zhengling Shang, Jiahong Wu
Summary: This study investigates the immunological impact of two mosquito saliva proteins on mast cells and proteases, finding that they can modulate mast cell-driven immune response and contribute to inflammatory reactions.
Article
Allergy
Stephen M. Hayes, Timothy C. Biggs, Simon P. Goldie, Philip G. Harries, Andrew F. Walls, Raymond N. Allan, Sylvia L. F. Pender, Rami J. Salib
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2020)
Article
Respiratory System
Prajakta Jogdand, Premkumar Siddhuraj, Michiko Mori, Caroline Sanden, Jimmie Jonsson, Andrew F. Walls, Jennifer Kearley, Alison A. Humbles, Roland Kolbeck, Leif Bjermer, Paul Newbold, Jonas S. Erjefalt
EUROPEAN RESPIRATORY JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Zhirong Fu, Srinivas Akula, Michael Thorpe, Lars Hellman
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Dermatology
Joanna Skrzeczynska-Moncznik, Katarzyna Zabieglo, Oktawia Osiecka, Agnieszka Morytko, Piotr Brzoza, Lukasz Drozdz, Monika Kapinska-Mrowiecka, Brice Korkmaz, Maciej Pastuszczak, Joanna Kosalka-Wegiel, Jacek Musial, Joanna Cichy
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2020)
Article
Cell Biology
Srinivas Akula, Aida Paivandy, Zhirong Fu, Michael Thorpe, Gunnar Pejler, Lars Hellman
Article
Biochemistry & Molecular Biology
Nathalie Gonska, Patricia A. Lopez, Paloma Lozano-Picazo, Michael Thorpe, Gustavo Guinea, Jan Johansson, Andreas Barth, Jose Perez-Rigueiro, Anna Rising
Article
Chemistry, Medicinal
Brice Korkmaz, Adam Lesner, Sylvain Marchand-Adam, Celia Moss, Dieter E. Jenne
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Cell Biology
Srinivas Akula, Aida Paivandy, Zhirong Fu, Michael Thorpe, Gunnar Pejler, Lars Hellman
Letter
Allergy
Timothy C. Biggs, Rana S. Abadalkareem, Stephen M. Hayes, Rebecca E. Holding, Laurie C. Lau, Philip G. Harries, Raymond N. Allan, Sylvia L. F. Pender, Andrew F. Walls, Rami J. Salib
Article
Biochemistry & Molecular Biology
Zhirong Fu, Srinivas Akula, Michael Thorpe, Lars Hellman
Summary: The efficiency of digestive endopeptidases in digesting folded proteins varies under different conditions. Pepsin is found to be more efficient in cleaving native folded proteins at low pH, while pancreatic enzymes primarily generate single amino acids or short peptides for absorption by the intestinal mucosa. Heat treatment improves cleavage by pancreatic enzymes, but acid treatment followed by neutral pH return does not significantly affect the process.
BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Ahlame Saidi, Mylene Wartenberg, Jean-Baptiste Madinier, Guy Ilango, Seda Seren, Brice Korkmaz, Fabien Lecaille, Vincent Aucagne, Gilles Lalmanach
Summary: The near-infrared fluorescent substrate-based probe (pro3-SBP) is a convenient tool for monitoring hPR3 activity, showing high specificity and sensitivity in detecting human neutrophil activation processes. It can be successfully hydrolyzed by activated human neutrophils and provides a strong signal under confocal microscopy.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Zhirong Fu, Srinivas Akula, Chang Qiao, Jinhye Ryu, Gurdeep Chahal, Lawrence de Garavilla, Jukka Kervinen, Michael Thorpe, Lars Hellman
Summary: Ruminants have developed a complex digestive system through gene duplications, particularly in the lysozyme c locus and chymase locus. The duplication of genes within these loci has allowed for flexibility in the ruminant digestive system, leading to specialization in food digestion.
Article
Biochemistry & Molecular Biology
Mark Damen, Mario A. Izidoro, Debora N. Okamoto, Lilian C. G. Oliveira, Helene I. Amatdjais-Groenen, Koen W. R. van Cleef, Ronald P. van Rij, Cindy E. J. Dieteren, Daniel Girones, Bernd N. M. van Buuren, Byron E. E. Martina, Albert D. M. E. Osterhaus, Luiz Juliano, Bob J. Scholte, Martin C. Feiters
Summary: This study reports the activity of lysine-based geminoid compounds against dengue virus infection by inhibiting proteases involved in viral replication. These compounds showed efficacy against both dengue virus protease and human furin protease, and also exhibited inhibitory effects on the replication of wildtype dengue virus. These findings could be promising for the development of antiviral therapeutics, not limited to dengue.
Review
Dermatology
Margo Waters, Allison Dobry, Stephanie T. Le, Kanade Shinkai, Thomas M. Beachkofsky, Mark D. P. Davis, Arturo R. Dominguez, Daniela Kroshinsky, Alina Markova, Robert G. Micheletti, Arash Mostaghimi, Helena B. Pasieka, Misha Rosenbach, Lucia Seminario-Vidal, John Trinidad, Joerg Albrecht, Emily M. Altman, Ryan Arakaki, Michael Arden-Jones, Alina G. Bridges, Adela R. Cardones, Angad A. Chadha, Jennifer K. Chen, Steven T. Chen, Kyle Cheng, Steven Daveluy, Katherine L. DeNiro, Joanna Harp, Jesse J. Keller, Brett King, Abraham M. Korman, Eve J. Lowenstein, Erin Luxenberg, Jennifer Brescoll Mancuso, Melissa M. Mauskar, Philip Milam, Kiran Motaparthi, Caroline A. Nelson, Cuong V. Nguyen, Fnu Nutan, Alex G. Ortega-Loayza, Tejesh Patel, Sahand Rahnama-Moghadam, Sergey Rekhtman, Nathan W. Rojek, Mansi Sarihan, Sheila Shaigany, Timmie R. Sharma, Sabrina M. Shearer, Bridget E. Shields, Lindsay C. Strowd, Danielle M. Tartar, Cristina Thomas, Karolyn A. Wanat, Andrew C. Walls, Lisa C. Zaba, Carolyn M. Ziemer, Emanual Maverakis, Benjamin H. Kaffenberger
Summary: This article discusses the importance of developing a skin-directed scoring system for EN, including consistent terminology and morphologic traits, as well as identifying the most affected sites. Through a Delphi consensus exercise, it was determined that there is a need for a skin-directed scoring system for EN.
Article
Biochemistry & Molecular Biology
Petter Berglund, Srinivas Akula, Zhirong Fu, Michael Thorpe, Lars Hellman
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)