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1.
J Biochem ; 167(6): 587-596, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-31960919

RESUMEN

Maintenance of cell surface residency and function of glycoproteins by lectins are essential for regulating cellular functions. Galectins are ß-galactoside-binding lectins and form a galectin-lattice, which regulates stability, clustering, membrane sub-domain localization and endocytosis of plasmalemmal glycoproteins. We have previously reported that galectin-2 (Gal-2) forms a complex with cationic amino acid transporter 3 (CAT3) in pancreatic ß cells, although the biological significance of the molecular interaction between Gal-2 and CAT3 has not been elucidated. In this study, we demonstrated that the structure of N-glycan of CAT3 was either tetra- or tri-antennary branch structure carrying ß-galactosides, which works as galectin-ligands. Indeed, CAT3 bound to Gal-2 using ß-galactoside epitope. Moreover, the disruption of the glycan-mediated bindings between galectins and CAT3 significantly reduced cell surface expression levels of CAT3. The reduced cell surface residency of CAT3 attenuated the cellular arginine uptake activities and subsequently reduced nitric oxide production, and thus impaired the arginine-stimulated insulin secretion of pancreatic ß cells. These results indicate that galectin-lattice stabilizes CAT3 by preventing endocytosis to sustain the arginine-stimulated insulin secretion of pancreatic ß cells. This provides a novel cell biological insight into the endocrinological mechanism of nutrition metabolism and homeostasis.


Asunto(s)
Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Galectina 2/metabolismo , Secreción de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Transducción de Señal/inmunología , Sistemas de Transporte de Aminoácidos Básicos/inmunología , Animales , Anticuerpos/inmunología , Arginina/metabolismo , Línea Celular Tumoral , Membrana Celular/metabolismo , Endocitosis/inmunología , Epítopos/metabolismo , Galactósidos/metabolismo , Galectina 2/inmunología , Lactosa/farmacología , Ligandos , Ratones , Óxido Nítrico/biosíntesis , Polisacáridos/metabolismo , Transducción de Señal/efectos de los fármacos
2.
Am J Trop Med Hyg ; 101(4): 851-858, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31392957

RESUMEN

Angiostrongyliasis is a foodborne disease caused by a zoonotic nematode, Angiostrongylus cantonensis, which produces eosinophilic meningitis or meningoencephalitis (EOM) in humans. Definitive diagnosis is rarely possible because worms are almost never recovered from patients. Human disease can be diagnosed by clinical symptoms and serological tests. Presently, diagnosis is performed by serological detection of antibodies against specific somatic antigens (molecular mass 29-31 kDa) extracted from female worms. The life cycle of A. cantonensis must be maintained in the laboratory to provide a source of this diagnostic antigen. Here, we cloned and expressed recombinant A. cantonensis galectin-2 (rAcGal2) corresponding to a 31-kDa antigenic peptide. Recombinant protein was purified and used in immunoblot tests, which showed reactions with human serum panels consisting of six confirmed angiostrongyliasis and 24 clinically diagnosed cases of EOM-associated with angiostrongyliasis, 160 samples from patients with other parasitic infections, and 30 samples from normal healthy subjects. Accuracy, sensitivity, specificity, and positive and negative predictive values were 95.0%, 93.3%, 95.3%, 75.7%, and 98.9%, respectively. The test was nonreactive with sera of human gnathostomiasis and cysticercosis, two diseases that could present similar neurological symptoms. Recombinant AcGal2 has potential as a diagnostic antigen and could replace native parasite antigens in further development of an angiostrongyliasis serodiagnostic test kit.


Asunto(s)
Angiostrongylus cantonensis/inmunología , Anticuerpos Antihelmínticos/sangre , Galectina 2/inmunología , Proteínas Recombinantes/inmunología , Infecciones por Strongylida/diagnóstico , Animales , Antígenos Helmínticos/inmunología , Humanos , Immunoblotting , Pruebas Serológicas
3.
Fish Shellfish Immunol ; 78: 238-247, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29678793

RESUMEN

Galectins are ß-galactoside binding lectins that play crucial roles in innate immunity in vertebrates and invertebrates through their conserved carbohydrate-recognition domains (CRDs). In the present study, single- and four-CRD-containing galectins were identified in oyster Crassostrea gigas (designated CgGal-2 and CgGal-3). The open reading frames (ORFs) of CgGal-2 and CgGal-3 encode polypeptides of 200 and 555 amino acids, respectively. All CRDs of CgGal-3 include two consensus motifs essential for ligand-binding, and a novel motif is present in CgGal-2. Pathogen-associated molecular pattern (PAMP) profiles were determined for recombinant rCgGal-2 and rCgGal-3, and rCgGal-2 displayed low binding affinity for PAMPs, while rCgGal-3 bound various PAMPs including glucan, lipopolysaccharide (LPS), and peptidoglycan (PGN) with relatively high affinity. Furthermore, rCgGal-2 and rCgGal-3 exhibited different microbe binding profiles; rCgGal-2 bound to Gram-negative bacteria (Escherichia coli and Vibrio vulnificus) and fungi (Saccharomyces cerevisiae and Pichia pastoris), while rCgGal-3 bound to these microbes but also to Gram-positive bacteria (Micrococcus luteus). In addition, rCgGal-3 possessed microbial agglutinating activity and coagulation activity against fungi and erythrocytes, respectively, but rCgGal-2 lacked any agglutinating activity. Carbohydrate binding specificity analysis showed that rCgGal-3 specifically bound D-galactose. Furthermore, rCgGal-2 and rCgGal-3 functioned as opsonin participating in the clearance against invaders in C. gigas. Thus, CgGal-2 with one CRD and CgGal-3 with four CRDs are new members of the galectin family involved in immune responses against bacterial infection. Differences in the organisation and amino acid sequences of CRDs may affect their specificity and affinity for nonself substances.


Asunto(s)
Crassostrea/genética , Galectina 2/genética , Galectina 3/genética , Regulación de la Expresión Génica/inmunología , Inmunidad Innata/genética , Secuencia de Aminoácidos , Animales , Crassostrea/inmunología , Hongos/fisiología , Galectina 2/química , Galectina 2/inmunología , Galectina 3/química , Galectina 3/inmunología , Perfilación de la Expresión Génica , Bacterias Gramnegativas/fisiología , Bacterias Grampositivas/fisiología , Filogenia , Alineación de Secuencia
4.
Cell Immunol ; 271(1): 97-103, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21724180

RESUMEN

Monocytes and macrophages link the innate and adaptive immune systems and protect the host from the outside world. In inflammatory disorders their activation leads to tissue damage. Galectins have emerged as central regulators of the immune system. However, if they regulate monocyte/macrophage physiology is still unknown. Binding of Gal-1, Gal-2, Gal-3 and Gal-4 to monocytes/macrophages, activation, cytokine secretion and apoptosis were determined by FACS, migration by Transwell system and phagocytosis by phagotest. Supernatants from macrophages co-cultured with galectins revealed their influence on T-cell function. In our study Gal-1, Gal-2, Gal-4, and partly Gal-3 bound to monocytes/macrophages. Galectins prevented Salmonella-induced MHCII upregulation. Cytokine release was distinctly induced by different galectins. T-cell activation was significantly restricted by supernatants of macrophages co-cultured in the presence of Gal-2 or Gal-4. Furthermore, all galectins tested significantly inhibited monocyte migration. Finally, we showed for the first time that galectins induce potently monocyte, but not macrophage apoptosis. Our study provides evidence that galectins distinctively modulate central monocyte/macrophage function. By inhibiting T-cell function via macrophage priming, we show that galectins link the innate and adaptive immune systems and provide new insights into the action of sugar-binding proteins.


Asunto(s)
Citocinas/inmunología , Galectinas/inmunología , Macrófagos/inmunología , Monocitos/inmunología , Apoptosis/inmunología , Unión Competitiva , Movimiento Celular/inmunología , Células Cultivadas , Citocinas/metabolismo , Citometría de Flujo , Galectina 1/inmunología , Galectina 1/metabolismo , Galectina 2/inmunología , Galectina 2/metabolismo , Galectina 3/inmunología , Galectina 3/metabolismo , Galectina 4/inmunología , Galectina 4/metabolismo , Galectinas/metabolismo , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Macrófagos/metabolismo , Monocitos/metabolismo , Fagocitosis/inmunología , Unión Proteica , Salmonella/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo
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