Article
Immunology
Patrick P. Mcdonald, Franziska Graf Leifer, Jessica Basso, Dan Lasala, Dedong Li, Kuan-Ju Chen, Jimin Zhang, Walter R. Perkins, David C. Cipolla
Summary: The efficacy of the DPP-1 inhibitor brensocatib was assessed in rat and mouse models, showing significant reduction in bone marrow NSP levels and improvement in disease score. In the mouse model, brensocatib even demonstrated similar efficacy to anti-TNF antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Jan E. Strobech, Pietro Giuriatti, Janine T. Erler
Summary: This review focuses on the role of neutrophils in regulating the extracellular matrix and how neutrophil-secreted proteases promote cancer metastasis.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Di Ren, Julia Fedorova, Kayla Davitt, Tran Ngoc Van Le, John H. Griffin, Patricia Chia-Ying Liaw, Charles Esmon, Alireza R. Rezaie, Ji Li
Summary: This study investigates the role of the APC-EPCR axis in ischemic insults in aging. The results show that APC activity is reduced during cardiac ischemia and reperfusion, and this reduction is more pronounced in aged hearts. Administration of APC prevents the shedding of EPCR induced by I/R and improves cardiac dysfunction in both young and aged mice. However, these cardioprotective effects of APC are diminished in EPCRR84A/R84A mice. AMPK mediates acute adaptive response while AKT is involved in chronic metabolic programming in APC-treated hearts.
CIRCULATION RESEARCH
(2022)
Article
Environmental Sciences
Karolina Nowak, Ewa Jablonska, Marzena Garley, Agnieszka Iwaniuk, Piotr Radziwon, Slawomir Wolczynski, Wioletta Ratajczak-Wronaa
Summary: This study investigated the estrogen-like effects and mechanism of action of commonly used parabens in human neutrophils. The results showed that parabens did not have cytotoxic effects on neutrophils, nor did they affect neutrophil functions or expression of estrogen receptors.
ENVIRONMENTAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Vadim Genkel, Ilya Dolgushin, Irina Baturina, Albina Savochkina, Karina Nikushkina, Anna Minasova, Lubov Pykhova, Veronika Sumerkina, Alla Kuznetsova, Igor Shaposhnik
Summary: This study aimed to investigate the diagnostic value of aging neutrophils in their relation to subclinical atherosclerosis in statin-naive patients without established atherosclerotic cardiovascular diseases (ASCVD). The results showed an increase in circulating CD62L(lo)CXCR4(hi)-neutrophils in statin-naive patients with subclinical atherosclerosis, and the increase demonstrated moderate diagnostic efficiency in relation to the detection of subclinical atherosclerosis, including polyvascular atherosclerosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
J. Morin-Genest, A. Saafane, D. Girard
Summary: Elimination of apoptotic neutrophils by macrophages is crucial for inflammation resolution. However, the fate and functionality of neutrophils aged in the absence of macrophages remain unclear. In this study, human neutrophils were aged in vitro and still retained the ability to generate reactive oxygen species, phagocytose, and adhere to a cell substratum. These findings suggest that a proportion of aged neutrophils may still exhibit biological functions during inflammation, when they are not efficiently eliminated by efferocytosis.
CELLULAR IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Exequiel O. J. Porta, Jaime A. Isern, Karunakaran Kalesh, Patrick G. Steel
Summary: In this study, a new therapeutic target for the treatment of leishmaniasis was discovered using an activity-based protein profiling strategy to investigate serine proteases (SPs) in Leishmania parasites. Significant differences in the expression levels of active Leishmania serine hydrolases (SHs) were observed throughout the parasite's life cycle and between different species. Two targetable SPs were identified in Leishmania mexicana using quantitative proteomic mass spectrometry. The results of this study provide templates for the discovery of new drugs for the treatment of leishmaniasis.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Physiology
Katlyn C. Richardson, Karen Jung, Julian Pardo, Christopher T. Turner, David J. Granville
Summary: Granzymes are serine proteases that were previously thought to have exclusive and redundant roles in lymphocyte-mediated cell death. However, recent studies have shown that each granzyme has distinct substrate profiles and functions, and their dysregulated proteolytic activities are associated with diverse pathologies.
Article
Immunology
Venkata Sita Rama Raju Allam, Ida Waern, Sowsan Taha, Srinivas Akula, Sara Wernersson, Gunnar Pejler
Summary: Asthma is characterized by an imbalance between proteases and their inhibitors. In this study, nafamostat, a serine protease inhibitor, showed to effectively suppress airway hyperreactivity, reduce inflammatory cell infiltration and pro-inflammatory compounds, and attenuate goblet cell hyperplasia and smooth muscle layer thickening in a mouse model of asthma. Transcriptomic analysis also revealed its suppression on pro-inflammatory gene expression, particularly those related to asthma. These findings suggest that nafamostat could be a potential therapeutic agent for human asthma.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Shuang Peng, Jian Gao, Darko Stojkov, Shida Yousefi, Hans-Uwe Simon
Summary: Neutrophils, the most abundant innate immune cells in human blood, have been overlooked in terms of their mitochondria function. However, growing evidence shows that mitochondria play a crucial role in various aspects of neutrophil biology, from development to chemotaxis, effector function, and cell death. Mitochondria and their components can also be released by neutrophils to eliminate infection and shape immune response. This review highlights the importance of mitochondria in modulating neutrophil phenotype and function during infection and inflammation, and discusses the potential and challenges of exploiting mitochondria in neutrophils for disease treatment.
IMMUNOLOGICAL REVIEWS
(2023)
Article
Chemistry, Medicinal
Daniels Jelisejevs, Anna Lina Bula, Linda Kinena
Summary: The study investigates /q- and y-lactams as electrophilic warheads for covalently targeting the Mpro active site at Cys145. The highest inhibitory activity was achieved using a pyrazolidinone warhead attached to the targeting dipeptide. Notably, the synergy between the warhead and the targeting dipeptide is crucial for the successful inhibition of Mpro.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Immunology
Bruno Rafael Pereira Lopes, Gabriel Soares da Silva, Gabriela de Lima Menezes, Juliana de Oliveira, Aripuana Sakurada Aranha Watanabe, Barbara Nery Porto, Roosevelt Alves da Silva, Karina Alves Toledo
Summary: This study found that serine proteases from neutrophil extracellular traps (NETs) interact and inactive human respiratory syncytial virus (hRSV). These results contribute to the understanding of the role of NETs in hRSV infection and designing treatment strategies for the inflammatory process during respiratory infections.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Editorial Material
Cell Biology
Brianna Cyr, Juan Pablo de Rivero Vaccari
Summary: The study investigates the effect of age on brain inflammation response, finding that older individuals exhibit more exacerbated inflammatory immune responses when faced with systemic infections.
Article
Immunology
Murtadha Q. Ali, Thomas P. Kohler, Gerhard Burchhardt, Andreas Wuest, Nadin Henck, Robert Bolsmann, Franziska Voss, Sven Hammerschmidt
Summary: This study revealed that pneumococcal serine proteases play a significant role in colonization but have a minor impact on pneumonia and invasive diseases.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Cell Biology
Noushin Saljoughian Esfahani, Qian Wu, Naresh Kumar, Latha Prabha Ganesan, William P. Lafuse, Murugesan V. S. Rajaram
Summary: Aging affects the phenotype and function of cardiac immune cells, leading to immune dysregulation and cardiac electrical dysfunction during infection in aged mice.