Article
Biochemistry & Molecular Biology
Li Hao, Aaron J. Marshall, Lixin Liu
Summary: Studies have shown that Bam32 plays a suppressive role in chemokine-induced neutrophil chemotaxis by regulating Rap1 activation and relies on the activation of the PI3K effector Akt.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Karolina A. P. Wijnands, Dennis M. Meesters, Benjamin Vandendriessche, Jacob J. Briede, Hans M. H. van Eijk, Peter Brouckaert, Anje Cauwels, Wouter H. Lamers, Martijn Poeze
Summary: Competition between NOS3 and NOS2 for arginine during endotoxemia appears crucial in the derangement of microcirculatory flow. This study found that L-citrulline supplementation enhances de novo arginine synthesis and NO production in mice during endotoxemia, especially in mice with functional NOS3-enzyme.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Xinhao Zhao, Le Yang, Na Chang, Lei Hou, Xuan Zhou, Chengbin Dong, Fuquan Liu, Lin Yang, Liying Li
Summary: This study identified that in chronic liver inflammation, the S1P/S1PRs system plays a crucial role in the recruitment of neutrophils. S1P enhances the migration and cytoskeletal remodeling of bone marrow (BM) neutrophils through S1PR(1) and S1PR(2), while the migration and cytoskeletal remodeling of dHL60 cells are mainly mediated by S1PR(2) and S1PR(3). Blocking S1PR(2) significantly reduces neutrophil infiltration in bile duct ligation (BDL)-induced mouse liver injury.
CELLULAR IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Sefik E. Erdener, Jianbo Tang, Kivilcim Kilic, Dmitry Postnov, John T. Giblin, Sreekanth Kura, I-Chun A. Chen, Tugberk Vayisoglu, Sava Sakadzic, Chris B. Schaffer, David A. Boas
Summary: Despite recanalization in acute ischemic stroke, less favorable outcomes may be attributed to the pathological phenomenon of dynamic flow stalls in cerebral capillaries. Modulation of these stalls can improve penumbral blood flow, oxygenation, reduce cellular damage, and improve functional outcomes after reperfusion. This dynamic microcirculatory stall phenomenon may contribute to ongoing penumbral injury and act as a potential hyperacute mechanism in ischemic stroke.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Cell Biology
Weiyang Li, Yuanru Yang, Lin Yang, Na Chang, Liying Li
Summary: This study reveals that bone marrow monocyte-derived Kupffer cells (MoKCs) dominate in injured livers. MoKCs exhibit enhanced proliferative and anti-apoptotic properties compared to embryonic KCs (EmKCs), promoting repair and attenuating fibrosis while reducing functional damage, necrosis, and fibrosis.
Article
Engineering, Biomedical
Yao Xiao, Chao Ren, Gan Chen, Pan Shang, Xiang Song, Guoxing You, Shaoduo Yan, Yongming Yao, Hong Zhou
Summary: This study explores the use of neutrophil membrane-mimicking nanodecoys (NM) as a biomimetic nanomedicine for the treatment of sepsis-associated liver injury. NM administration shows excellent biocompatibility and effectively reduces inflammatory cytokines and liver injury biomarkers, reduces hepatic malondialdehyde content and myeloperoxidase activity, and improves survival in a septic mouse model. In vitro studies also demonstrate that NM neutralizes neutrophil chemokines and inflammatory mediators, and mitigates neutrophil chemotaxis and adhesion. NM also attenuates lipopolysaccharide-induced reactive oxygen species generation, cyclooxygenase-2 expression, nitric oxide secretion, and subsequent hepatocyte injury. This study provides a promising therapeutic strategy for sepsis-induced acute liver injury.
MATERIALS TODAY BIO
(2022)
Article
Multidisciplinary Sciences
Arthur Lau, Jennifer J. Rahn, Mona Chappellaz, Hyunjae Chung, Hallgrimur Benediktsson, Dominique Bihan, Anne von Massenhausen, Andreas Linkermann, Craig N. Jenne, Stephen M. Robbins, Donna L. Senger, Ian A. Lewis, Justin Chun, Daniel A. Muruve
Summary: This study reveals the role of DPEP1 as a major leukocyte adhesion receptor in the kidney and a potential therapeutic target for AKI.
Article
Gastroenterology & Hepatology
Naroa Goikoetxea-Usandizaga, Miren Bravo, Leire Egia-Mendikute, Leticia Abecia, Marina Serrano-Macia, Rocio G. Urdinguio, Marc Clos-Garcia, Ruben Rodriguez-Agudo, Raquel Araujo-Legido, Lucia Lopez-Bermudo, Teresa C. Delgado, Sofia Lachiondo-Ortega, Irene Gonzalez-Recio, Claudia Gil-Pitarch, Ainize Pena-Cearra, Jorge Simon, Raquel Benede-Ubieto, Silvia Arino, Jose M. Herranz, Mikel Azkargorta, Julio Salazar-Bermeo, Nuria Marti, Marta Varela-Rey, Juan M. Falcon-Perez, Oscar Lorenzo, Ruben Nogueiras, Felix Elortza, Yulia A. Nevzorova, Francisco J. Cubero, Domingo Saura, Luis Alfonso Martinez-Cruz, Guadalupe Sabio, Asis Palazon, Pau Sancho-Bru, Natalia Elguezabal, Mario F. Fraga, Matias A. Avila, Ramon Bataller, Jose J. G. Marin, Franz Martin, Maria Luz Martinez-Chantar
Summary: Alcohol-associated liver disease (ALD), accounting for 70% of liver-related deaths in Europe, has no effective approved therapies. However, targeting methylation-controlled J protein (MCJ) may help in recovering mitochondrial fitness without collateral oxidative damage. Liver-specific MCJ silencing can prevent major ALD hallmarks, such as mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, improving lipid metabolism and liver injury.
Review
Immunology
Ananda N. Rankin, Skyler Hendrix, Sumanta K. Naik, Christina L. Stallings
Summary: Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection and the disease outcome is influenced by the host's immune response. Neutrophils, especially low-density neutrophils (LDNs), play important roles in TB and are associated with disease severity in TB and other lung infections.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Cell Biology
Shi-Peng Li, Xin-Qiang Li, Xiao-Jie Chen, Jin-Ming Zhang, Guang-Peng Zhou, Liu-Xin Zhou, Hai-Ming Zhang, Li-Ying Sun, Zhi-Jun Zhu
Summary: This study investigated the proinflammatory cytokines and differentially expressed proteins in a mouse model of liver transplantation using a protein chip system and proteomics. Bioinformatics analysis was employed to analyze the immune response activation-associated network. The results revealed significant changes in cytokine levels and identified key proteins associated with liver transplant rejection. These findings provide new insights and potential treatment targets for liver transplant rejection.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Article
Biochemistry & Molecular Biology
Hernando Gomez, Hakon Haugaa, Daniel Escobar, Ana M. Botero, Rachel Pool, Gaspar Del Rio-Pertuz, Carlos L. Manrique-Caballero, Lisa Gordon, Alicia Frank, Jean-Louis Teboul, Brian S. Zuckerbraun, Michael R. Pinsky
Summary: The study found that guiding resuscitation based on macrohemodynamics during endotoxemic shock cannot predict tissue metabolic stress and microvascular response to resuscitation, nor can it prevent tubular injury and AKI. Microvascular flow index, PCO2 gap, and P(v-a)CO2/C(a-v)O-2 ratio outperformed macrohemodynamic parameters in predicting renal metabolic stress and tubular injury, suggesting potential as resuscitation targets.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Multidisciplinary Sciences
Giovanna Vella, Felix Ritzmann, Lisa Wolf, Andreas Kamyschnikov, Hannah Stodden, Christian Herr, Hortense Slevogt, Robert Bals, Christoph Beisswenger
Summary: Neutrophilic inflammation in COPD is exacerbated by gram-negative bacteria like nontypeable Haemophilus influenzae and cigarette smoke. IL-17C, an inflammatory cytokine expressed by airway epithelial cells, promotes harmful pulmonary inflammation in COPD triggered by bacteria. IL-17C deficiency in mice leads to decreased neutrophil numbers in lungs exposed to both NTHi and CS, but does not protect from CS-induced lung inflammation. A preliminary patient study suggests that IL-17C levels in sputum samples correlate with COPD disease severity, particularly in advanced stages.
Review
Gastroenterology & Hepatology
Matthew J. McConnell, Enis Kostallari, Samar H. Ibrahim, Yasuko Iwakiri
Summary: LSECs are a unique population of endothelial cells in the liver, playing a crucial role in liver homeostasis and disease. Recent advancements in single-cell analysis have improved our understanding of LSEC heterogeneity, aging, regenerative capacity, and their involvement in liver inflammation. This review also explores the role of LSECs in various liver pathologies and highlights the gaps in knowledge for future research.
Article
Multidisciplinary Sciences
Adriana A. de Jesus, Guibin Chen, Dan Yang, Tomas Brdicka, Natasha M. Ruth, David Bennin, Dita Cebecauerova, Hana Malcova, Helen Freeman, Neil Martin, Karel Svojgr, Murray H. Passo, Farzana Bhuyan, Sara Alehashemi, Andre T. Rastegar, Katsiaryna Uss, Lela Kardava, Bernadette Marrero, Iris Duric, Ebun Omoyinmi, Petra Peldova, Chyi-Chia Richard Lee, David E. Kleiner, Colleen M. Hadigan, Stephen M. Hewitt, Stefania Pittaluga, Carmelo Carmona-Rivera, Katherine R. Calvo, Nirali Shah, Miroslava Balascakova, Danielle L. Fink, Radana Kotalova, Zuzana Parackova, Lucie Peterkova, Daniela Kuzilkova, Vit Campr, Lucie Sramkova, Angelique Biancotto, Stephen R. Brooks, Cameron Manes, Eric Meffre, Rebecca L. Harper, Hyesun Kuehn, Mariana J. Kaplan, Paul Brogan, Sergio D. Rosenzweig, Melinda Merchant, Zuoming Deng, Anna Huttenlocher, Susan L. Moir, Douglas B. Kuhns, Manfred Boehm, Karolina Skvarova Kramarzova, Raphaela Goldbach-Mansky
Summary: Neutrophilic inflammation is a common feature in many genetic autoinflammatory diseases. This study presents three cases of newborns with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation, and identified novel variants in the Src-family tyrosine kinase LYN that lead to Lyn kinase activation. The research highlights the critical role of Lyn kinase in modulating inflammatory signals, regulating microvascular permeability, neutrophil recruitment, and promoting hepatic fibrosis.
NATURE COMMUNICATIONS
(2023)
Review
Immunology
Yi Wang, Cheng-long Zhu, Peng Li, Qiang Liu, Hui-ru Li, Chang-meng Yu, Xiao-ming Deng, Jia-feng Wang
Summary: Sepsis is a life-threatening dysfunction caused by an uncontrolled host response to infection, leading to respiratory dysfunction and acute respiratory distress syndrome (ARDS). Neutrophils, the first line of defense against infection, play a major role in sepsis. However, studies have shown that despite high levels of chemokines at the site of infection, neutrophils cannot migrate properly and instead accumulate in the lungs, causing tissue damage and ARDS. Dysregulation of chemokine receptors, particularly G protein-coupled receptors (GPCRs), is implicated in impaired neutrophil migration. This review summarizes the signaling pathways and mechanisms by which GPCR dysfunction in sepsis leads to impaired neutrophil chemotaxis and proposes potential targets for intervention to improve neutrophil chemotaxis.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Raymond Shim, Connie H. Y. Wong
BRAIN BEHAVIOR AND IMMUNITY
(2018)
Review
Cell Biology
Kathryn Prame Kumar, Alyce J. Nicholls, Connie H. Y. Wong
CELL AND TISSUE RESEARCH
(2018)
Article
Hematology
Shu Wen Wen, Connie H. Y. Wong
Article
Hematology
Annas Al-Sharea, Man K. S. Lee, Alexandra Whillas, Danielle L. Michell, Waled A. Shihata, Alyce J. Nicholls, Olivia D. Cooney, Michael J. Kraakman, Camilla Bertuzzo Veiga, Ann-Maree Jefferis, Kristy Jackson, Prabhakara R. Nagareddy, Gavin Lambert, Connie H. Y. Wong, Karen L. Andrews, Geoff A. Head, Jaye Chin-Dusting, Andrew J. Murphy
Article
Cell Biology
Shu Wen Wen, Raymond Shim, Luke Ho, Brooke J. Wanrooy, Yogitha N. Srikhanta, Kathryn Prame Kumar, Alyce J. Nicholls, S. J. Shen, Tara Sepehrizadeh, Michael de Veer, Velandai K. Srikanth, Henry Ma, Thanh G. Phan, Dena Lyras, Connie H. Y. Wong
Article
Clinical Neurology
Raymond Shim, Shu Wen Wen, Brooke J. Wanrooy, Michelle Rank, Tharani Thirugnanachandran, Luke Ho, Tara Sepehrizadeh, Michael de Veer, Velandai K. Srikanth, Henry Ma, Thanh G. Phan, Christopher G. Sobey, Connie H. Y. Wong
TRANSLATIONAL STROKE RESEARCH
(2020)
Review
Neurosciences
Kathryn Prame Kumar, Connie H. Y. Wong
CURRENT OPINION IN NEUROBIOLOGY
(2020)
Article
Immunology
Mujun Sun, Rhys D. Brady, Brooke Wanrooy, Richelle Mychasiuk, Glenn R. Yamakawa, Pablo M. Casillas-Espinosa, Connie H. Y. Wong, Sandy R. Shultz, Stuart J. McDonald
JOURNAL OF NEUROIMMUNOLOGY
(2020)
Article
Cell Biology
Maria Selvadurai, Mitchell J. Moon, Simon J. Mountford, Xiao Ma, Zhaohua Zheng, Ian G. Jennings, Natasha M. Setiabakti, Rizani P. Iman, Rose J. Brazilek, Nurul Aisha Z. Abidin, Gaetan Chicanne, Sonia Severin, Alyce J. Nicholls, Connie H. Y. Wong, Jean-Yves Rinckel, Anita Eckly, Christian Gachet, Warwick S. Nesbitt, Philip E. Thompson, Justin R. Hamilton
SCIENCE TRANSLATIONAL MEDICINE
(2020)
Editorial Material
Immunology
Connie H. Y. Wong, Craig N. Jenne, Elzbieta Kolaczkowska
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Immunology
Sj Shen, Kathryn Prame Kumar, Shu Wen Wen, Raymond Shim, Brooke J. Wanrooy, Dragana Stanley, Robert J. Moore, Thi Thu Hao Van, Remy Robert, Michael J. Hickey, Connie H. Y. Wong
Summary: Ulcerative colitis is associated with colonic neutrophil accumulation, and recent studies suggest that dietary fiber deficiency can promote an inflammatory state in the colon. Supplementing with acetate, a short-chain fatty acid produced through bacterial fermentation of dietary fiber, can protect against colonic neutrophil enrichment and pathology in an experimental model of colitis.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Brooke J. Wanrooy, Shu Wen Wen, Connie H. Y. Wong
Summary: Research on neutrophils in the neuroinflammatory cascade after ischemic stroke indicates their diverse roles in the acute stages, potentially eliciting both pro-inflammatory and anti-inflammatory effects. The uncertainty regarding the benefits or harms of neutrophil diversity in stroke remains, but if their hypothesized wound-healing functions can be validated, it may provide a promising therapeutic target for the majority of stroke patients currently without treatment.
IMMUNOLOGY AND CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Samuel A. Mills, Andrew Jobling, Michael A. Dixon, Bang Bui, Kirstan A. Vessey, Joanna A. Phipps, Ursula Greferath, Gene Venables, Vickie H. Y. Wong, Connie H. Y. Wong, Zheng He, Flora Hui, James C. Young, Josh Tonc, Elena Ivanova, Botir T. Sagdullaev, Erica L. Fletcher
Summary: Local blood flow control within the central nervous system (CNS) is dependent on coordination between neurons, glia, and blood vessels. This study explored the role of microglia in retinal vasoregulation, showing that microglia actively participate in the neurovascular unit and contribute to vascular compromise during diabetic retinopathy. The findings suggest that aberrant microglial-vascular function may play a role in early vascular changes in diabetic retinopathy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Brooke J. Wanrooy, Shu Wen Wen, Raymond Shim, Jenny L. Wilson, Kathryn Prame Kumar, Connie Hy Wong
Summary: Previous studies have conflicting results regarding the recruitment of innate immune cells after cerebral ischemia. This study used different cell markers to evaluate the contributions of these cells and their inflammatory states. The results showed that brain-associated innate immune cells display various stroke-induced inflammatory states that depend on the experimental stroke setting.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Hematology
ZheHao Tan, Pam Hall, Adam Costin, Simon A. Crawford, Georg Ramm, Connie H. Y. Wong, A. Richard Kitching, Michael J. Hickey
Summary: The role of the endothelial surface layer (ESL) in recruiting monocytes and neutrophils in glomerular capillaries is unclear. This study shows that the ESL does not modulate the trafficking and retention of these immune cells in both steady-state and acutely-inflamed glomeruli.