Myeloid cells are tunable by a polyanionic polysaccharide derivative and co-determine host rescue from lethal virus infection

Autor: Jozef Van Damme, Nele Berghmans, Alfons Billiau, Erik Martens, Hubertine Heremans, Mieke Gouwy, Ghislain Opdenakker, C Dillen, Melissa van Pel, Nathalie Lamerant-Fayel, Claudine Kieda, Sofie Starckx, Willem E. Fibbe, Sandra Li
Přispěvatelé: Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Jazyk: angličtina
Rok vydání: 2010
Předmět:
CXC CHEMOKINES
Chemokine
Viral pathogenesis
Immunology
MENGO-VIRUS
Biology
Antiviral Agents
Virus
03 medical and health sciences
Mice
0302 clinical medicine
GRANULOCYTE CHEMOTACTIC PROTEIN-2
Polysaccharides
Chemokine CXCL6
Mengovirus
INTERFERON-PRODUCTION
Cardiovirus Infections
Leukocytes
Immunology and Allergy
Animals
Humans
Myeloid Cells
RNA
Messenger
MACROPHAGE INFLAMMATORY PROTEIN-2
IN-VIVO
030304 developmental biology
0303 health sciences
Innate immune system
Effector
Chemotaxis
ANTIVIRAL ACTIVITY
Viral Vaccines
neutrophils recruitment GCP-2 antiviral encephalomyelitis COAM granulocyte chemotactic protein-2 chlorite-oxidized oxyamylose macrophage inflammatory protein-2 antiviral activity in-vivo interferon-production mengo-virus cxc chemokines gelatinase b mice
Cell Biology
biology.organism_classification
3. Good health
Cell biology
Virus Diseases
030220 oncology & carcinogenesis
biology.protein
Cytokines
Amylose
CHLORITE-OXIDIZED OXYAMYLOSE
GELATINASE B
Zdroj: Journal of Leukocyte Biology, 88(5), 1017-1029
Journal of Leukocyte Biology
Journal of Leukocyte Biology, Society for Leukocyte Biology, 2010, 88 (5), pp.1017-1029. ⟨10.1189/jlb.1109724⟩
ISSN: 1017-1029
0741-5400
DOI: 10.1189/jlb.1109724⟩
Popis: Chlorite-oxidized oxyamylose protects in a model of acute lethal virus infection with chemo-attracted phagocytes as antiviral leukocytes. Insight into molecular and cellular mechanisms of innate immunity is critical to understand viral pathogenesis and immunopathology and might be exploited for therapy. Whereas the molecular mechanisms of the IFN defense are well established, cellular mechanisms of antiviral immunity are only emerging, and their pharmacological triggering remains unknown. COAM is a polysaccharide derivative with antiviral activity but without comprehension about its mechanism of action. The COAM mixture was fractionated, and prophylactic treatment of mice with COAM polymers of high MW resulted in a conversion from 100% lethal mengovirus infection to an overall survival rate of 93% without obvious clinical sequelae. Differential and quantitative analysis of peritoneal leukocytes demonstrated that COAM induced a profound influx of neutrophils. Selective cell depletion experiments pointed toward neutrophils and macrophages as key effector cells in the rescue of mice from lethal mengovirus. COAM was able to induce mRNA and protein expression of the mouse neutrophil chemokine GCP-2. Binding of GCP-2 to COAM was demonstrated in solution and confirmed by SPR technology. Although COAM was not chemotactic for neutrophils, COAM-anchored muGCP-2 retained chemotactic activity for human and mouse neutrophils. In conclusion, this study established that COAM rescued mice from acute and lethal mengovirus infection by recruiting antiviral leukocytes to the site of infection, as proposed through the induction, binding, and concentration of endogenous chemokines. These findings reinforce the role of neutrophils and macrophages as critical cells that can be manipulated toward antiviral defense.
Databáze: OpenAIRE
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