Article
Immunology
Deborah L. W. Chong, Carine Rebeyrol, Ricardo J. Jose, Andrew E. Williams, Jeremy S. Brown, Chris J. Scotton, Joanna C. Porter
Summary: Neutrophil migration into the lung is mediated by cell adhesion molecules such as ICAM-1 and ICAM-2, which are upregulated during inflammatory stimulation. While beta(2) integrins interacting with ICAMs may regulate neutrophil traffic in healthy lung, these interactions may become redundant later in inflammation when epithelial junctions are disrupted.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Lai Wen, Alex Marki, Zhihao Wang, Marco Orecchioni, Jeffrey Makings, Monica Billitti, Erpei Wang, Sujit S. A. Suthahar, Kenneth Kim, William B. Kiosses, Zbigniew Mikulski, Klaus Ley
Summary: This study generated a humanized beta(2) integrin knockin mouse model to study its in vivo activation. The results showed that beta(2) integrins play an important role in leukocyte recruitment and neutrophil adhesion.
Article
Biochemistry & Molecular Biology
Max L. B. Gronloh, Janine J. G. Arts, Sebastian Palacios Martinez, Amerens A. van Der Veen, Lanette Kempers, Abraham C. van Steen, Joris J. T. H. Roelofs, Martijn A. Nolte, Joachim Goedhart, Jaap D. van Buul
Summary: Using a photoconvertible probe, researchers traced and identified the original endothelial transmigration hotspots, and found that these hotspots function to limit vascular leakage during transmigration events. The distribution of ICAM-1 determines the location of the transmigration hotspot.
Article
Biology
Natalia Alves De Matos, Onesia Cristina Oliveira Lima, Josiane Fernandes Da Silva, Annie Rocio Pineros, Juliana Carvalho Tavares, Virginia Soares Lemos, Jose Carlos Alves-Filho, Andre Klein
Summary: PAR2 plays an important role in mediating allergic airway inflammation by modulating cytokine production and vascular permeability. PAR2 blockade can reduce the recruitment of eosinophils and neutrophils, as well as decrease the levels of inflammatory markers. PAR2-activating peptide acts synergistically with ovalbumin to promote eosinophil recruitment into bronchoalveolar lavage fluid and increase certain cytokine levels in lymph nodes.
JOURNAL OF BIOSCIENCES
(2022)
Article
Immunology
Mona Singh, Mony Thakur, Manish Mishra, Manisha Yadav, Rajkamal Vibhuti, Athira M. Menon, Girima Nagda, Ved Prakash Dwivedi, Tikam Chand Dakal, Vinod Yadav
Summary: ICAM-1 is a key inducible cell adhesion molecule involved in immune functions, with its expression regulated by various inflammatory mediators such as transcription factors and signaling pathways. Transcriptional regulation and epigenetic modifications play important roles in controlling ICAM-1 expression.
IMMUNOLOGY LETTERS
(2021)
Article
Medical Laboratory Technology
Varinder Singh, Rupinder Kaur, Pratima Kumari, Chirag Pasricha, Ravinder Singh
Summary: Leukocyte migration is vital for lymphocyte recirculation and immune response. ICAM-1 and VCAM-1 play a crucial role in leukocyte adherence to endothelial cells in various diseases. They contribute to inflammation, leukocyte migration, and have implications in multiple pathological states. Understanding their immunoregulatory role and pathophysiological effects helps in disease management.
CLINICA CHIMICA ACTA
(2023)
Article
Immunology
Anna Barkaway, Loic Rolas, Regis Joulia, Jennifer Bodkin, Tchern Lenn, Charlotte Owen-Woods, Natalia Reglero-Real, Monja Stein, Laura Vazquez-Martinez, Tamara Girbl, Robin N. Poston, Matthew Golding, Rebecca S. Saleeb, Aude Thiriot, Ulrich H. von Andrian, Johan Duchene, Mathieu-Benoit Voisin, Cleo L. Bishop, David Voehringer, Axel Roers, Antal Rot, Tim Laemmermann, Sussan Nourshargh
Summary: Aging is associated with dysregulated immune functions, affecting neutrophil diapedesis. In aged mice, neutrophils exhibit reverse transendothelial migration, causing remote organ damage.
Article
Medicine, Research & Experimental
Adel Abo Mansour, Federica Raucci, Mustafa Sevim, Anella Saviano, Jenefa Begum, Zhaogong Zhi, Laleh Pezhman, Samantha Tull, Francesco Maione, Asif Jilani Iqbal
Summary: This study investigates the role of Gal-9 in the migration and adhesion of CD4+ and CD8+ T cells and reveals its potential therapeutic significance in inflammatory-based diseases. The findings suggest that Gal-9 supports T cell adhesion and transmigration in a glycan dependent manner and inhibits the chemotactic function of CXCL12 through direct binding.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Immunology
Thomas M. Martin, Susan J. Burke, Clive H. Wasserfall, J. Jason Collier
Summary: ICAM-1 plays a crucial role in the development of type 1 diabetes by participating in immune responses and cell adhesion and activation. Understanding the mechanisms of ICAM-1 is essential for controlling glucose homeostasis.
AUTOIMMUNITY REVIEWS
(2023)
Review
Cardiac & Cardiovascular Systems
Carina Mauersberger, Julia Hinterdobler, Heribert Schunkert, Thorsten Kessler, Hendrik B. Sager
Summary: This article comprehensively reviews the process of leukocyte recruitment relevant to atherosclerosis, with a focus on endothelial cells, monocytes and macrophages, neutrophils, T lymphocytes and platelets. Therapeutic options targeting leukocyte recruitment into atherosclerotic lesions, as well as potential insights into its precise mechanisms, are also highlighted.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Oncology
Yang Xiao, Jinghong Chen, Jia Wang, Wei Guan, Mengzhen Wang, Linlin Zhang, Zhiding Wang, Lixin Wang, Li Yu
Summary: In patients with AML, the expression of ICAM-1 is silenced, but the hypomethylating agent can upregulate its expression, facilitating NK cells to kill AML cells. High expression of ICAM-1 can reverse AML immune evasion and activate NK cell function, suggesting a new strategy for AML treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Tamar Kapanadze, Jaba Gamrekelashvili, Stefan Sablotny, Dustin Kijas, Hermann Haller, Kai Schmidt-Ott, Florian P. Limbourg
Summary: Ischemia induces an inflammatory response involving monocyte-derived macrophages (MF) that contribute to angiogenesis and tissue repair. Notch signaling, mediated by Notch ligand Delta-like 1 (Dll1), plays a role in regulating angiogenesis and ischemic macrophage differentiation. Colony stimulating factor 1 (CSF-1) is essential for MF lineage development, but its interaction with Notch signaling in ischemic macrophage development is not well understood.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Carla Cunha, Catarina Leite Pereira, Joana R. Ferreira, Claudia Ribeiro-Machado, Sibylle Grad, Susana G. Santos, Raquel M. Goncalves
Summary: This study evaluated the therapeutic potential of a chemoattractant delivery system for intervertebral disc (IVD) and found that it has the ability to recruit more cells, but no evidence of IVD regeneration was observed. Systemic injection of mesenchymal stem cells (MSCs) may play a role in IVD regeneration to some extent, but no synergies were observed when combined with the chemoattractant delivery system. Further exploration is needed before successful clinical translation of IVD regeneration using this strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Regis Joulia, Idaira Maria Guerrero-Fonseca, Tamara Girbl, Jonathon A. Coates, Monja Stein, Laura Vazquez-Martinez, Eleanor Lynam, James Whiteford, Michael Schnoor, David Voehringer, Axel Roers, Sussan Nourshargh, Mathieu-Benoit Voisin
Summary: This study reveals that perivascular mast cells regulate the final steps of neutrophil diapedesis through the outer pericyte layer via IL-17A production, potentially providing insights for inflammatory disorders driven by increased neutrophil diapedesis.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Jan Dudeck, Johanna Kotrba, Roland Immler, Aaron Hoffmann, Martin Voss, Vasileia Ismini Alexaki, Lorena Morton, Stephan Rene Jahn, Konstantinos Katsoulis-Dimitriou, Simon Winzer, Georg Kollias, Thomas Fischer, Sergei A. Nedospasov, Ildiko Rita Dunay, Triantafyllos Chavakis, Andreas J. Mueller, Burkhart Schraven, Markus Sperandio, Anne Dudeck
Summary: Mast cell-derived tumor necrosis factor is crucial for neutrophil extravasation by promoting intraluminal crawling and provides a potential target for therapeutic approaches.
Article
Chemistry, Multidisciplinary
Tarik Bozoglu, Seungmin Lee, Tilman Ziegler, Victoria Jurisch, Sanne Maas, Andrea Baehr, Rabea Hinkel, Amelie Hoenig, Anjana Hariharan, Christina Inyeop Kim, Simon Decker, Haider Sami, Tobias Koppara, Ruppert Oellinger, Oliver J. Muller, Derk Frank, Remco Megens, Peter Nelson, Christian Weber, Angelika Schnieke, Markus Sperandio, Gianluca Santamaria, Roland Rad, Alessandra Moretti, Karl-Ludwig Laugwitz, Oliver Soehnlein, Manfred Ogris, Christian Kupatt
Summary: The study demonstrates a method of retargeting adeno-associated viruses (AAVs) to endothelial cells by coating them with second-generation polyamidoamine dendrimers (G2) linked to endothelial-affine peptides (CNN). This approach improves gene transfer efficiency, potentially enabling applications in vascular and atherosclerosis models.
Article
Hematology
Qiuyue Ma, Roland Immler, Monika Pruenster, Markus Sellmayr, Chenyu Li, Albrecht von Brunn, Brigitte von Brunn, Rosina Ehmann, Roman Woelfel, Matteo Napoli, Qiubo Li, Paola Romagnani, Ralph Thomas Boettcher, Markus Sperandio, Hans-Joachim Anders, Stefanie Steiger
Summary: This study investigates the impact of uric acid on neutrophils and finds that hyperuricemia impairs neutrophil function. Partial reduction of uric acid levels using uricase can partially restore the neutrophil defects. The study reveals that uric acid affects neutrophil migration by regulating intracellular pH and cytoskeletal dynamics. These findings have important implications for understanding immunodeficiency in kidney disease and sterile inflammation.
Article
Immunology
Martin Bernhard Mueller, Max Huebner, Lei Li, Stephanie Tomasi, Valena Liesske, David Effinger, Simon Hirschberger, Kristin Pogoda, Markus Sperandio, Simone Kreth
Summary: This study reveals a novel regulatory network in which miR-125a acts as a central hub to regulate endothelial barrier permeability and monocyte migration. The network involves the modulation of adhesion molecules, phosphatases, and transcription factors, leading to the opening of the endothelial barrier. Furthermore, miR-125a enhances the expression of a chemokine in endothelial cells, while suppressing its own expression in monocytes, resulting in enhanced monocyte chemotaxis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Thomas Bromberger, Sarah Klapproth, Markus Sperandio, Markus Moser
Summary: The use of cell-based reporter systems has provided valuable insights into the molecular mechanisms of integrin activation. The generation of a Hoxb8 cell line expressing human beta 2 integrin that functionally replaced the deleted mouse ortholog has overcome the limitations of current models. These cells can be stimulated by physiological stimuli, leading to conformational changes in beta 2 integrin.
Editorial Material
Physiology
Markus Sperandio
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fitsumbirhan T. Mehari, Meike Miller, Robert Pick, Almke Bader, Kami Pekayvaz, Matteo Napoli, Bernd Uhl, Christoph A. Reichel, Markus Sperandio, Barbara Walzog, Christian Schulz, Steffen Massberg, Konstantin Stark
Summary: The study demonstrated the activation and migration patterns of leukocytes during inflammation through intravital microscopy and signal analysis. The researchers identified distinct calcium signaling patterns in different cell types and revealed key molecules involved in regulating these patterns. This study provides new insights into the assessment of leukocyte activation and migration during inflammation.
Article
Immunology
Zhi Ma, Huixia Yang, Mirjana Kessler, Markus Sperandio, Sven Mahner, Udo Jeschke, Viktoria von Schoenfeldt
Summary: Carbohydrate Lewis antigens and related glycosyltransferases are dysregulated in the decidua of patients with unexplained recurrent miscarriage. The gene FUT3 is responsible for the synthesis of sLeA in the endometrium and affects endometrial receptivity. Targeting the aberrantly elevated sLeA may be a potential therapy for inappropriate implantation in unexplained recurrent miscarriage.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Reproductive Biology
Zhi Ma, Mirjana Kessler, Anca Chelariu-Raicu, Markus Sperandio, Sven Mahner, Udo Jeschke, Viktoria von Schoenfeldt
Summary: The expression of sLeX in the receptive endometrium is enhanced by IL-1 beta, facilitating trophoblast adhesion during embryo implantation. This study provides important insights into the molecular mechanisms of embryo implantation.
BIOLOGY OF REPRODUCTION
(2023)
Article
Immunology
Sergi Masgrau-Alsina, Lou Martha Wackerbarth, Dae-sik Lim, Markus Sperandio
Summary: This study identifies MST1 as a critical regulator of neutrophil homeostasis and mobilization from the bone marrow, shedding light on its complex role in regulating innate immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Ina Rohwedder, Lou Martha Wackerbarth, Kristina Heinig, Annamaria Ballweg, Johannes Altstaetter, Myriam Ripphahn, Claudia Nussbaum, Melanie Salvermoser, Susanne Bierschenk, Tobias Straub, Matthias Gunzer, Marc Schmidt-Supprian, Thomas Kolben, Christian Schulz, Averil Ma, Barbara Walzog, Matthias Heinig, Markus Sperandio
Summary: Newborns, especially premature infants, are prone to developing neonatal sepsis due to differences in immune system requirements during intrauterine and extrauterine life. Through transcriptomic analysis, we have identified the molecular mechanisms of neutrophil maturation and functional adaptation in fetal ontogeny. Our findings reveal constitutive activation of the noncanonical NF-KB pathway and upregulation of A20 in fetal neutrophils, leading to appropriate adaptation of neutrophil function during intrauterine fetal life but potentially hampering immune responses in prematurely born infants.
Article
Immunology
Aikaterini Gatsiou, Simon Tual-Chalot, Matteo Napoli, Almudena Ortega-Gomez, Tommy Regen, Rachit Badolia, Valeriana Cesarini, Claudia Garcia-Gonzalez, Raphael Chevre, Giorgia Ciliberti, Carlos Silvestre-Roig, Maurizio Martini, Jedrzej Hoffmann, Rana Hamouche, Joseph R. Visker, Nikolaos Diakos, Astrid Wietelmann, Domenico Alessandro Silvestris, Georgio Georgiopoulos, Ali Moshfegh, Andre Schneider, Wei Chan, Stefan Guenther, Johanne Backs, Shin Kwak, Craig H. Selzman, Kimon Stamatelopoulos, Stefan Rose-John, Christian Trautwein, Ioakim Spyridopoulos, Thomas Braun, Ari Waisman, Angela Gallo, Stavros G. Drakos, Stefanie Dimmeler, Markus Sperandio, Oliver Soehnlein, Konstantinos Stellos
Summary: RNA editor ADAR2 regulates endothelial responses to IL-6, controlling leukocyte trafficking in inflamed and ischemic tissues. ADAR2 is required for IL-6 trans-signaling and immune cell infiltration through suppressing primary microRNA processing.
Review
Medicine, General & Internal
Sebastian Sitaru, Agnes Budke, Riccardo Bertini, Markus Sperandio
Summary: Mounting experimental evidence suggests that the CXCL8-CXCR1/2 axis plays an essential role in neutrophils in the pathophysiology of inflammatory, autoimmune, and neoplastic diseases. Therapeutic targeting of CXCR1/2 or CXCL8 has been extensively studied using in vitro and animal disease models, showing potential benefits for patients with unwanted neutrophil-mediated inflammation. However, careful evaluation is needed for the use of inhibitors in severe infections or sepsis. Inhibition of the CXCL8-CXCR1/2 axis also holds promise for cancer therapy, with ongoing efforts to define its involvement in neoplastic diseases.
INTERNAL AND EMERGENCY MEDICINE
(2023)
Article
Allergy
Selina K. Jorch, Annika McNally, Philipp Berger, Jonas Wolf, Kim Kaiser, Andrian Chetrusca Covash, Stefanie Robeck, Isabell Pastau, Olesja Fehler, Saskia-L. Jauch-Speer, Sven Hermann, Michael Schafers, Hanne Van Gorp, Apurva Kanneganti, Joke Dehoorne, Filomeen Haerynck, Federica Penco, Marco Gattorno, Jae Jin Chae, Paul Kubes, Mohamed Lamkanfi, Andy Wullaert, Markus Sperandio, Thomas Vogl, Johannes Roth, Judith Austermann
Summary: This study provides evidence that S100A8/A9 alarmins are released through a pyrin/caspase-1/gasdermin D-dependent pathway in FMF patients, and they directly drive autoimmune inflammation in vivo.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Monika Pruenster, Roland Immler, Jonas Roth, Tim Kuchler, Thomas Bromberger, Matteo Napoli, Katrin Nussbaumer, Ina Rohwedder, Lou Martha Wackerbarth, Chiara Piantoni, Konstantin Hennis, Diana Fink, Sebastian Kallabis, Tobias Schroll, Sergi Masgrau-Alsina, Agnes Budke, Wang Liu, Dietmar Vestweber, Christian Wahl-Schott, Johannes Roth, Felix Meissner, Markus Moser, Thomas Vogl, Veit Hornung, Petr Broz, Markus Sperandio
Summary: This study elucidates the mechanisms of S100A8/S100A9 release from neutrophils, revealing that E-selectin regulates the release of S100A8/S100A9 through NLRP3 and gasdermin D. This process serves as a rapid and reversible activation system that plays a crucial role in inflammation.
Article
Multidisciplinary Sciences
Won Ho Yang, Peter V. Aziz, Douglas M. Heithoff, Yeolhoe Kim, Jeong Yeon Ko, Jin Won Cho, Michael J. Mahan, Markus Sperandio, Jamey D. Marth
Summary: The colonic mucosal barrier provides protection against infection, inflammation, and tissue ulceration. The erosion of this barrier is a common feature of colitis, but the underlying molecular mechanisms are not well understood. This study used a food poisoning model to investigate the erosion of the mucosal barrier. The findings suggest that previous infection activates an innate immune mechanism that leads to the activation of Neu3 neuraminidase in colonic epithelial cells and increased secretion of Cathepsin-G protease by Paneth cells. These host responses, combined with the desialylation of Mucin-2, render the mucosal barrier susceptible to proteolytic breakdown. Inhibiting Cathepsin-G or Neu3 function can protect against proteolysis and barrier erosion, reducing the frequency and severity of colitis.