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Your search keyword '"CD33-RELATED SIGLECS"' showing total 3 results
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3 results on '"CD33-RELATED SIGLECS"'

1. Host and pathogen hyaluronan signal through human siglec-9 to suppress neutrophil activation

Author

Secundino, Ismael, Lizcano, Anel, Roupé, K Markus, Wang, Xiaoxia, Cole, Jason N, Olson, Joshua, Ali, S Raza, Dahesh, Samira, Amayreh, Lenah K, Henningham, Anna, Varki, Ajit, and Nizet, Victor

Subjects
Medicinal and Biomolecular Chemistry, Chemical Sciences, Clinical Research, Emerging Infectious Diseases, Infectious Diseases, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, 2.2 Factors relating to the physical environment, Animals, Antigens, CD, Apoptosis, Bacteria, Chemotaxis, Leukocyte, Extracellular Traps, Gene Expression, Host-Pathogen Interactions, Humans, Hyaluronic Acid, Immunity, Innate, Immunoglobulin Fc Fragments, Molecular Weight, Neutrophil Activation, Neutrophils, Protein Binding, Protein Interaction Domains and Motifs, Recombinant Fusion Proteins, Respiratory Burst, Sialic Acid Binding Immunoglobulin-like Lectins, Streptococcus, CD33-related Siglecs, Hyaluronan, Group A Streptococcus, Immunology, Medicinal and biomolecular chemistry
Abstract

UnlabelledInhibitory CD33-related Siglec receptors regulate immune cell activation upon engaging ubiquitous sialic acids (Sias) on host cell surface glycans. Through molecular mimicry, Sia-expressing pathogen group B Streptococcus binds inhibitory human Siglec-9 (hSiglec-9) to blunt neutrophil activation and promote bacterial survival. We unexpectedly discovered that hSiglec-9 also specifically binds high molecular weight hyaluronan (HMW-HA), another ubiquitous host glycan, through a region of its terminal Ig-like V-set domain distinct from the Sia-binding site. HMW-HA recognition by hSiglec-9 limited neutrophil extracellular trap (NET) formation, oxidative burst, and apoptosis, defining HMW-HA as a regulator of neutrophil activation. However, the pathogen group A Streptococcus (GAS) expresses a HMW-HA capsule that engages hSiglec-9, blocking NET formation and oxidative burst, thereby promoting bacterial survival. Thus, a single inhibitory lectin receptor detects two distinct glycan "self-associated molecular patterns" to maintain neutrophil homeostasis, and two leading human bacterial pathogens have independently evolved molecular mimicry to exploit this immunoregulatory mechanism.Key messageHMW-HA is the first example of a non-sialic acid containing glycan to be recognized by CD33-related Siglecs. HMW-HA engagement of hSiglec-9 attenuates neutrophil activation. Group A Streptococcus exploits hSiglec-9 recognition via its polysaccharide HMW-HA capsule to subvert neutrophil killing.

Published
2016

2. Soluble Siglec-5 associates to PSGL-1 and displays anti-inflammatory activity

Author

Pepin, Marion, Mezouar, Soraya, Pegon, Julie, Muczynski, Vincent, Adam, Frédéric, Bianchini, Elsa P, Bazaa, Amine, Proulle, Valerie, Rupin, Alain, Paysant, Jerome, Panicot-Dubois, Laurence, Christophe, Olivier D., Dubois, Christophe, Lenting, Peter J, Denis, Cécile V, Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Université Paris-Sud - Paris 11 (UP11)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut de Recherches Internationales Servier [Suresnes] (IRIS), The study was financially supported by a PhD-research grant from Institut Servier & Association Nationale de la Recherche Technique (Contrat CIFRE) to JPe, and an Inserm-Poste d’Accueil-grant (# ASC13101LSA) to MP., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Anti-Inflammatory Agents/pharmacology, E-SELECTIN LIGAND-1, [SDV]Life Sciences [q-bio], Anti-Inflammatory Agents, MESH: Membrane Glycoproteins/genetics, MESH: Antigens, Differentiation, Myelomonocytic/metabolism, MESH: Lectins/metabolism, MESH: Antigens, CD/pharmacology, MESH: Leukocytes, Mononuclear/drug effects, Lectins, MESH: Animals, MYELOID CELLS, MESH: E-Selectin/metabolism, NEUTROPHILS, IN-VIVO, MESH: Inflammation/drug therapy, Membrane Glycoproteins, MESH: Inflammation/chemically induced, MESH: Inflammation/pathology, MESH: Membrane Glycoproteins/metabolism, MESH: Leukocyte Rolling/physiology, P-Selectin, Female, E-Selectin, MESH: Leukocytes, Mononuclear/metabolism, CD33-RELATED SIGLECS, VON-WILLEBRAND-FACTOR, MESH: Lectins/pharmacology, Antigens, Differentiation, Myelomonocytic, MESH: Antigens, Differentiation, Myelomonocytic/pharmacology, MESH: Tumor Necrosis Factor-alpha/toxicity, GLYCOPROTEIN LIGAND, MESH: Antigens, CD/metabolism, Article, MESH: Mice, Inbred C57BL, Antigens, CD, Animals, Humans, Leukocyte Rolling, Protein Interaction Domains and Motifs, MESH: Antigens, Differentiation, Myelomonocytic/genetics, SIALIC-ACID, Inflammation, MESH: Protein Interaction Domains and Motifs, MESH: Humans, Tumor Necrosis Factor-alpha, MESH: Lectins/genetics, MESH: Solubility, Mice, Inbred C57BL, Disease Models, Animal, Solubility, Leukocytes, Mononuclear, MESH: Antigens, CD/genetics, IMMUNE-SYSTEM, MESH: Disease Models, Animal, MESH: Female, MESH: P-Selectin/metabolism
Abstract

International audience; Interactions between endothelial selectins and the leukocyte counter-receptor PSGL1 mediates leukocyte recruitment to inflammation sites. PSGL1 is highly sialylated, making it a potential ligand for Siglec-5, a leukocyte-receptor that recognizes sialic acid structures. Binding assays using soluble Siglec-5 variants (sSiglec-5/C4BP and sSiglec-5/Fc) revealed a dose- and calcium-dependent binding to PSGL1. Pre-treatment of PSGL1 with sialidase reduced Siglec-5 binding by 79 ± 4%. In confocal immune-fluorescence assays, we observed that 50% of Peripheral Blood Mononuclear Cells (PBMCs) simultaneously express PSGL1 and Siglec-5. Duolink-proximity ligation analysis demonstrated that PSGL1 and Siglec-5 are in close proximity (

Published
2016
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3. Host and pathogen hyaluronan signal through human siglec-9 to suppress neutrophil activation

Author

Ismael Secundino, Xiaoxia Wang, S. Raza Ali, Joshua Olson, Anel Lizcano, Anna Henningham, Ajit Varki, Lenah K. Amayreh, Samira Dahesh, K. Markus Roupé, Victor Nizet, and Jason N. Cole

Subjects
0301 basic medicine, Neutrophils, Gene Expression, Apoptosis, Plasma protein binding, medicine.disease_cause, Extracellular Traps, Neutrophil Activation, Drug Discovery, Innate, Sialic Acid Binding Immunoglobulin-like Lectins, Hyaluronic Acid, Genetics (clinical), CD33-related Siglecs, Hyaluronan, Respiratory Burst, Host cell surface, biology, Chemotaxis, Group A Streptococcus, food and beverages, CD, Molecular mimicry, Chemotaxis, Leukocyte, Infectious Diseases, Host-Pathogen Interactions, Molecular Medicine, Infection, Protein Binding, Glycan, Recombinant Fusion Proteins, 1.1 Normal biological development and functioning, Immunology, Article, Microbiology, 03 medical and health sciences, Medicinal and Biomolecular Chemistry, Antigens, CD, Clinical Research, Underpinning research, medicine, Animals, Humans, Protein Interaction Domains and Motifs, Antigens, Neutrophil homeostasis, Bacteria, Immunity, SIGLEC, Streptococcus, Neutrophil extracellular traps, Leukocyte, Immunity, Innate, Immunoglobulin Fc Fragments, Molecular Weight, 030104 developmental biology, biology.protein
Abstract

UnlabelledInhibitory CD33-related Siglec receptors regulate immune cell activation upon engaging ubiquitous sialic acids (Sias) on host cell surface glycans. Through molecular mimicry, Sia-expressing pathogen group B Streptococcus binds inhibitory human Siglec-9 (hSiglec-9) to blunt neutrophil activation and promote bacterial survival. We unexpectedly discovered that hSiglec-9 also specifically binds high molecular weight hyaluronan (HMW-HA), another ubiquitous host glycan, through a region of its terminal Ig-like V-set domain distinct from the Sia-binding site. HMW-HA recognition by hSiglec-9 limited neutrophil extracellular trap (NET) formation, oxidative burst, and apoptosis, defining HMW-HA as a regulator of neutrophil activation. However, the pathogen group A Streptococcus (GAS) expresses a HMW-HA capsule that engages hSiglec-9, blocking NET formation and oxidative burst, thereby promoting bacterial survival. Thus, a single inhibitory lectin receptor detects two distinct glycan "self-associated molecular patterns" to maintain neutrophil homeostasis, and two leading human bacterial pathogens have independently evolved molecular mimicry to exploit this immunoregulatory mechanism.Key messageHMW-HA is the first example of a non-sialic acid containing glycan to be recognized by CD33-related Siglecs. HMW-HA engagement of hSiglec-9 attenuates neutrophil activation. Group A Streptococcus exploits hSiglec-9 recognition via its polysaccharide HMW-HA capsule to subvert neutrophil killing.

Published
2016

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