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Alexander Gluschko, Marc Herb, Katja Wiegmann, Oleg Krut, Wolfram F Neiss, Olaf Utermöhlen, Martin Krönke, Michael Schramm
The intracellular pathogen Listeria monocytogenes (L.m.) is targeted by the autophagic machinery, but the molecular mechanisms involved and consequences for anti-listerial immunity remain enigmatic. Here, we demonstrate that L.m. infection of macrophages in vivo exclusively evokes LC3-associated phagocytosis (LAP), but not canonical autophagy, and that targeting of L.m. by LAP is required for anti-listerial immunity. The pathway leading to LAP induction in response to L.m. infection emanates from the β2 integrin Mac-1 (CR3, integrin αM β2 ), a receptor recognizing diverse microbial ligands...
March 14, 2018: Cell Host & Microbe
Valeryi K Lishko, Valentin P Yakubenko, Tatiana P Ugarova, Nataly P Podolnikova
Platelet Factor 4 (PF4) is one of the most abundant cationic proteins secreted from α-granules of activated platelets. Based on its structure, PF4 was assigned to the CXC family of chemokines and has been shown to have numerous effects on myeloid leukocytes. However, the receptor for PF4 remains unknown. Here, we demonstrate that PF4 induces leukocyte responses through the integrin Mac-1 (αM β2 , CD11b/CD18). Human neutrophils, monocytes, U937 monocytic and HEK293 cells expressing Mac-1 strongly adhered to immobilized PF4 in a concentration-dependent manner...
March 14, 2018: Journal of Biological Chemistry
Nathalia Regina F Leal, Mariana Vieira Vigliano, Fabiana A Pinto, Thayane V de Sousa, Leosvaldo S M Velozo, Kátia C C Sabino, Maria da Graça Justo, Marsen Garcia Pinto Coelho
OBJECTIVES: To evaluate the anti-inflammatory potential of Pterodon polygalaeflorus hexane extract (HE) and its fractions on macrophage migration in vitro and in vivo. METHODS: Hexane extract from P. polygalaeflorus fruits was fractionated and yielded four fractions. RAW 264.7 cells were treated with samples to evaluate cell viability (MTT assay), cell migration (wound healing and transwell assays), CD14 expression (flow cytometry), iNOS and cytokine mRNA expression (RT-qPCR), NO (Griess reaction) and cytokine (ELISA) production...
March 7, 2018: Journal of Pharmacy and Pharmacology
Vijay K Juneja, Tim B Mohr, Meryl Silverman, O Peter Snyder
The objective of this study was to assess the ability of Bacillus cereus spores to germinate and grow in order to determine a safe cooling rate for cooked rice, beans, and pasta, rice-chicken (4:1), rice-chicken-vegetables (3:1:1), rice-beef (4:1), and rice-beef-vegetables (3:1:1). Samples were inoculated with a cocktail of four strains of heat-shocked (80°C for 10 min) B. cereus spores (NCTC 11143, 935A/74, Brad 1, and Mac 1) to obtain a final spore concentration of approximately 2 log CFU/g. Thereafter, samples were exponentially cooled through the temperature range of 54...
February 23, 2018: Journal of Food Protection
Edward F Plow, Yunmei Wang, Daniel I Simon
Current antithrombotic drugs, including widely used antiplatelet agents and anticoagulants, are associated with significant bleeding risk, which increases morbidity and mortality. Nevertheless, there is emerging experimental evidence that suggests that the molecular and cellular mechanisms of hemostasis and thrombosis can be separated, thereby raising the possibility of new antithrombotic therapeutic targets with reduced bleeding risk. We summarize some recently emerging examples of agents with antithrombotic activities that seem to spare hemostasis...
February 21, 2018: Blood
Mojca Frank-Bertoncelj, David S Pisetsky, Christoph Kolling, Beat A Michel, Renate E Gay, Astrid Jüngel, Steffen Gay
Extracellular vesicles (EV) can modulate the responses of cells to toll-like receptor (TLR) ligation; conversely, TLR ligands such as double-stranded RNA (dsRNA) can enhance the release of EV and influence of the composition and functions of EV cargos. Inflamed synovial joints in rheumatoid arthritis (RA) are rich in EV and extracellular RNA; besides, RNA released from necrotic synovial fluid cells can activate the TLR3 signaling in synovial fibroblasts (SFs) from patients with RA. Since EV occur prominently in synovial joints in RA and may contribute to the pathogenesis, we questioned whether EV can interact with dsRNA, a TLR3 ligand, and modify its actions in arthritis...
2018: Frontiers in Immunology
Shao-Xia Chen, Shao-Kun Wang, Pei-Wen Yao, Guang-Jie Liao, Xiao-Dong Na, Yong-Yong Li, Wei-An Zeng, Xian-Guo Liu, Ying Zang
Previous work from our laboratory showed that motor nerve injury by lumbar 5 ventral root transection (L5-VRT) led to interleukin-6 (IL-6) overexpression in bilateral spinal cord, and that intrathecal administration of IL-6 neutralizing antibody delayed the induction of mechanical allodynia in bilateral hind paws. However, early events and upstream mechanisms underlying spinal IL-6 expression following L5-VRT require elucidation. The model of L5-VRT was used to induce neuropathic pain, which was assessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats...
February 9, 2018: Journal of Neurochemistry
Farid Boulad, Tsiporah Shore, Koen van Besien, Caterina Minniti, Mihaela Barbu-Stevanovic, Sylvie Wiener Fedus, Fabiana Perna, June Greenberg, Danielle Guarneri, Vijay Nandi, Audrey Mauguen, Karina Yazdanbakhsh, Michel Sadelain, Patricia A Shi
Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cell harvest for transduction or gene editing. We therefore performed a Phase I dose-escalation study of the hematopoietic progenitor cell mobilizing agent plerixafor to evaluate the efficacy and safety of standard dosing on peripheral blood CD34+ cell mobilization. Of 15 patients enrolled to date, only one was chronically transfused and 10 were on hydroxyurea. Of 8 patients achieving a CD34+ cell concentration >30 cells/μl, 6 were on hydroxyurea...
February 1, 2018: Haematologica
Dennis Wolf, Nathaly Anto-Michel, Hermann Blankenbach, Ansgar Wiedemann, Konrad Buscher, Jan David Hohmann, Bock Lim, Marina Bäuml, Alex Marki, Maximilian Mauler, Daniel Duerschmied, Zhichao Fan, Holger Winkels, Daniel Sidler, Philipp Diehl, Dirk M Zajonc, Ingo Hilgendorf, Peter Stachon, Timoteo Marchini, Florian Willecke, Maximilian Schell, Björn Sommer, Constantin von Zur Muhlen, Jochen Reinöhl, Teresa Gerhardt, Edward F Plow, Valentin Yakubenko, Peter Libby, Christoph Bode, Klaus Ley, Karlheinz Peter, Andreas Zirlik
Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo...
February 6, 2018: Nature Communications
Lee Seung-Jin
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Ning Li, Hao Yang, Manliu Wang, Shouqin Lü, Yan Zhang, Mian Long
Lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1), and their counter-receptors such as intercellular cell adhesion molecule (ICAM)-1 and ICAM-2, junctional adhesion molecule (JAM)-A, JAM-C and receptor for advanced glycation end products (RAGE) are crucial to promote polymorphonuclear leukocyte (neutrophil, PMN) recruitment. The underlying mechanisms of ligand-specific bindings in this cascade remain incompletely known. We compared the dynamic force spectrum for various LFA-1/Mac-1-ligand bonds using single molecule atomic force microscopy (AFM) and tested their functions to mediate PMN recruitment under in vitro shear flow...
December 27, 2017: Molecular Biology of the Cell
Junko Yano, Brian M Peters, Mairi C Noverr, Paul L Fidel
For over 3 decades, investigators have studied the pathogenesis of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) through clinical studies and animal models. While there was considerable consensus that susceptibility was not associated with any apparent deficiencies in adaptive immunity, protective immune mechanisms and the role of innate immunity remained elusive. It was not until an innovative live-challenge design was conducted in women that a fuller understanding of the natural history of infection/disease was achieved...
March 2018: Infection and Immunity
Wensheng Chen, Darrell Pilling, Richard H Gomer
BACKGROUND: Pentraxins are a family of highly conserved secreted proteins that regulate the innate immune system, including monocytes and macrophages. C-reactive protein (CRP) is a plasma protein whose levels can rise to 1000 μg/ml from the normal <3 μg/ ml during inflammation. RESULTS: We find that CRP inhibits proliferation of the human myeloid leukemia cell line Mono Mac 6 with an IC50 of 75 μg/ ml by inducing apoptosis of these cells. The related proteins serum amyloid P (SAP) and pentraxin 3 (PTX3) do not inhibit Mono Mac 6 proliferation...
December 4, 2017: BMC Immunology
Chunyan Chen, Tingting Li, Yuchen Zhao, Yinfeng Qian, Xiaoyi Li, Xiangrong Dai, Dake Huang, Tianzhong Pan, Lanlan Zhou
Blood-brain barrier (BBB) disruption, thrombus formation and immune-mediated inflammation are important steps in the pathophysiology of cerebral ischemia-reperfusion injury but are still inaccessible to therapeutic interventions. Recent studies have provided increasing evidence that blocking of platelet glycoprotein (GP) receptor Ib might represent a novel target in treating acute ischemic stroke. This research was conducted to explore the therapeutic efficacy and potential mechanisms of GPIbα inhibitor (anfibatide) in a model of brain ischemia-reperfusion injury in mice...
November 28, 2017: Brain, Behavior, and Immunity
Jakub Novák, Ivo Fabrik, Irena Linhartová, Marek Link, Ondřej Černý, Jiří Stulík, Peter Šebo
The adenylate cyclase toxin (CyaA) of the whooping cough agent Bordetella pertussis subverts immune functions of host myeloid cells expressing the αM β2 integrin (CD11b/CD18, CR3 or Mac-1). CyaA delivers into cytosol of cells an extremely catalytically active adenylyl cyclase enzyme, which disrupts the innate and adaptive immune functions of phagocytes through unregulated production of the key signaling molecule cAMP. We have used phosphoproteomics to analyze cAMP signaling of CyaA in murine bone marrow-derived dendritic cells...
November 24, 2017: Scientific Reports
Xiao Zhang, Linda Li, Ning Li, Xinyu Shu, Lüwen Zhou, Shouqin Lü, Shenbao Chen, Debin Mao, Mian Long
The functional performance of αI domain α7 helix in β2 integrin activation depends on the allostery of the α7 helix, which axially slides down; therefore, it is critical to elucidate what factors regulate the allostery. In this study, we determined that there were two conservative salt bridge interaction pairs that constrain both the upper and bottom ends of the α7 helix. Molecular Dynamics (MD) simulations for three β2 integrin members of LFA-1 (αL β2 ), Mac-1 (αM β2 ) and αx β2 indicated that the magnitude of the salt bridge interaction is related to the stability of the αI domain and the strength of the corresponding force-induced allostery...
November 18, 2017: FEBS Journal
Tamar Tak, Tomasz P Rygiel, Guruswamy Karnam, Okan W Bastian, Louis Boon, Marco Viveen, Frank E Coenjaerts, Linde Meyaard, Leo Koenderman, Janesh Pillay
Severe influenza virus infection can lead to life-threatening pathology through immune-mediated tissue damage. In various experimental models, this damage is dependent on T-cells. There is conflicting evidence regarding the role of neutrophils in influenza-mediated pathology. Neutrophils are often regarded as cells causing tissue damage, but in recent years it has become clear that a subset of human neutrophils is capable of suppressing T-cells, which is dependent on Mac-1 (CD11b/CD18). Therefore, we tested the hypothesis that immune suppression by neutrophils can reduce T-cell mediate pathology after influenza infection...
November 15, 2017: American Journal of Respiratory Cell and Molecular Biology
Jan M Herter, Andreas Margraf, Stephanie Volmering, Benedito Eduardo Correia, J Michael Bradshaw, Angelina Bisconte, Ronald J Hill, Claire L Langrish, Clifford A Lowell, Alexander Zarbock
BACKGROUND AND PURPOSE: Following inflammatory stimuli neutrophils are recruited to sites of inflammation and exert effector functions that often have deleterious effects on tissue integrity, which can lead to organ failure. Btk is expressed in neutrophils, and constitutes a promising pharmacological target for neutrophil mediated tissue damage. Here we evaluate a selective reversible inhibitor of the Bruton's tyrosine kinase (PRN473) for its ability to dampen neutrophil influx via inhibition of adhesion receptor signaling pathways...
November 11, 2017: British Journal of Pharmacology
Xiuli An, Lixiang Chen
To study the process of erythropoiesis, it is important to be able to isolate erythroid progenitors and erythroblasts at distinct stages of development. During the past decade, considerable progress has been made on the development of flow cytometry (FCM) and fluorescence-activated cell sorting (FACS) methods for the analysis and isolation of both murine and human erythroid cells at distinct stages of erythropoiesis, based on changes in the expression of cell surface markers. A method for the identification of murine BFU-E and CFU-E cells was reported by Flygare et al...
2018: Methods in Molecular Biology
Sandro Félix Perazzio, Paulo Vitor Soeiro-Pereira, Viviane Cardoso Dos Santos, Marlon Vilela de Brito, Bruno Salu, Maria Luiza Vilela Oliva, Anne Margherite Stevens, Alexandre Wagner Silva de Souza, Hans D Ochs, Troy R Torgerson, Antonio Condino-Neto, Luis Eduardo Coelho Andrade
BACKGROUND: Studies have suggested that soluble factors in plasma from patients with active (aBD) and inactive (iBD) Behçet's disease (BD) stimulate neutrophil function. Soluble CD40 ligand (sCD40L) is an important mediator of inflammation in BD. Its expression and effect on neutrophil oxidative burst and neutrophil extracellular trap (NET) release have not been characterized. In this study, we sought to investigate the role of plasma and the CD40L pathway on NET release and the oxidative burst profile in patients with aBD and iBD...
October 19, 2017: Arthritis Research & Therapy
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