RESUMEN
Mushrooms were considered as a special delicacy by early civilizations and valued as a credible source of nutrients including considerable amounts of dietary fiber, minerals, and vitamins (in particularly, vitamin D). Mushrooms are also recognized as functional foods for their bioactive compounds offer huge beneficial impacts on human health. One of those potent bioactives is ß-glucan, comprising a backbone of glucose residues linked by ß-(1â3)-glycosidic bonds with attached ß-(1â6) branch points, which exhibits antitumor and immunostimulating properties. The commercial pharmaceutical products from this polysaccharide source, such as schizophyllan, lentinan, grifolan, PSP (polysaccharide-peptide complex) and PSK (polysaccharide-protein complex), have shown evident clinical results. The immunomodulating action of mushroom polysaccharides is to stimulate natural killer cells, T-cells, B-cells, neutrophils, and macrophage dependent immune system responses via differing receptors involving dectin-1, the toll-like receptor-2 (a class of proteins that play a role in the immune system), scavengers and lactosylceramides. ß-Glucans with various structures present distinct affinities toward these receptors to trigger different host responses. Basically, their antitumor abilities are influenced by the molecular mass, branching configuration, conformation, and chemical modification of the polysaccharides. This review aims to integrate the information regarding nutritional, chemical and biological aspects of polysaccharides in mushrooms, which will possibly be employed to elucidate the correlation between their structural features and biological functions.
Asunto(s)
Agaricales/química , Antineoplásicos , Polisacáridos , Adyuvantes Inmunológicos/farmacología , Humanos , Factores Inmunológicos , Lectinas Tipo C/efectos de los fármacos , Lectinas Tipo C/fisiología , Lentinano , Polisacáridos/química , Polisacáridos/farmacología , Proteoglicanos , Sizofirano , Relación Estructura-Actividad , Receptor Toll-Like 2/efectos de los fármacos , Receptor Toll-Like 2/fisiología , beta-Glucanos/química , beta-Glucanos/farmacologíaAsunto(s)
Antígenos de Neoplasias/fisiología , Biomarcadores de Tumor/fisiología , Hepatitis/tratamiento farmacológico , Lectinas Tipo C/fisiología , Fallo Hepático/tratamiento farmacológico , Acetaminofén/toxicidad , Enfermedad Aguda , Animales , Antígenos de Neoplasias/efectos adversos , Antígenos de Neoplasias/uso terapéutico , Biomarcadores de Tumor/efectos adversos , Biomarcadores de Tumor/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Hepatitis/etiología , Humanos , Lectinas Tipo C/uso terapéutico , Regeneración Hepática , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Estudios Multicéntricos como Asunto , Proteínas Asociadas a Pancreatitis , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Receptor fas/agonistasRESUMEN
Islet Neogenesis-Associated Protein (INGAP) is a member of the Reg family of proteins implicated in various settings of endogenous pancreatic regeneration. The expression of INGAP and other RegIII proteins has also been linked temporally and spatially with the induction of islet neogenesis in animal models of disease and regeneration. Furthermore, administration of a peptide fragment of INGAP (INGAP peptide) has been demonstrated to reverse chemically induced diabetes as well as improve glycemic control and survival in an animal model of type 1 diabetes. Cultured human pancreatic tissue has also been shown to be responsive to INGAP peptide, producing islet-like structures with function, architecture and gene expression matching that of freshly isolated islets. Likewise, studies in normoglycemic animals show evidence of islet neogenesis. Finally, recent clinical studies suggest an effect of INGAP peptide to improve insulin production in type 1 diabetes and glycemic control in type 2 diabetes.
Asunto(s)
Antígenos de Neoplasias/fisiología , Biomarcadores de Tumor/fisiología , Islotes Pancreáticos/fisiología , Lectinas Tipo C/fisiología , Regeneración/fisiología , Animales , Antígenos de Neoplasias/farmacología , Biomarcadores de Tumor/farmacología , Ensayos Clínicos Fase II como Asunto , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Evaluación Preclínica de Medicamentos , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/fisiología , Proteínas Asociadas a Pancreatitis , Regeneración/efectos de los fármacosRESUMEN
Lectins comprise a family of related proteins that mediate essential cell functions through binding to carbohydrates. Within this protein family, C-type lectins are defined by the requirement of calcium for optimal biologic activity. Using reverse transcription PCR, a cDNA corresponding to a putative C-type lectin has been amplified from the hookworm parasite Ancylostoma ceylanicum. The 550 nucleotide open reading frame of the A. ceylanicum C-type Lectin-1 (AceCTL-1) cDNA corresponds to a 167 amino acid mature protein (18,706 Da) preceded by a 17 amino acid secretory signal sequence. The recombinant protein (rAceCTL-1) was expressed in Drosophila S2 cells and purified using a combination of affinity chromatography and reverse phase HPLC. Using in vitro carbohydrate binding studies, it was determined that rAceCTL-1 binds N-acetyl-d-glucosamine, a common component of eukaryotic egg cell membranes. Using a polyclonal IgG raised against the recombinant protein, the native AceCTL-1 was identified in sperm and soluble protein extracts of adult male A. ceylanicum by immunoblot. Probing of adult hookworm sections with the polyclonal IgG demonstrated localization to the testes in males, as well as the spermatheca and developing embryos in females, consistent with its role as a sperm protein. Together, these data strongly suggest that AceCTL-1 is a male gender-specific C-type lectin with a function in hookworm reproductive physiology.
Asunto(s)
Ancylostoma/química , Anquilostomiasis/parasitología , Clonación Molecular , Proteínas del Helminto/fisiología , Lectinas Tipo C/fisiología , Secuencia de Aminoácidos , Ancylostoma/genética , Ancylostoma/fisiología , Animales , Cricetinae , ADN Complementario , Femenino , Proteínas del Helminto/química , Proteínas del Helminto/genética , Lectinas Tipo C/química , Lectinas Tipo C/genética , Masculino , Mesocricetus , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Reproducción , Alineación de SecuenciaRESUMEN
The Islet Neogenesis Associated Protein (INGAP) increases pancreatic beta-cell mass and potentiates glucose-induced insulin secretion. We currently studied the effects of a pentadecapeptide having the 104-118 amino acid sequence of INGAP (INGAP-PP) on insulin secretion and on transcript profile expression in 4-day-cultured normal pancreatic neonatal rat islets. Islets cultured with INGAP-PP released significantly more insulin in response to 2.8 and 16.7 mM glucose than those cultured without the peptide. The macroarray analysis showed that 210 out of 2352 genes spotted in the nylon membranes were up-regulated while only 4 were down-regulated by INGAP-PP-treatment. The main categories of genes modified by INGAP-PP included several related with islet metabolism, insulin secretion mechanism, beta-cell mass and islet neogenesis. RT-PCR confirmed the macroarray results for ten selected genes involved in growing, maturation, maintenance of pancreatic islet-cells, and exocytosis, i.e., Hepatocyte nuclear factor 3beta (HNF3beta), Upstream stimulatory factor 1 (USF1), K(+)-channel proteins (SUR1 and Kir6.2), PHAS-I protein, Insulin 1 gene, Glucagon gene, Mitogen-activated protein kinase 1 (MAP3K1), Amylin (IAPP), and SNAP-25. INGAP-PP also stimulated PDX-1 expression. The expression of three transcripts (HNF3beta, SUR1, and SNAP-25) was confirmed by Western blotting for the corresponding proteins. In conclusion, our results show that INGAP-PP enhances specifically the secretion of insulin and the transcription of several islet genes, many of them directly or indirectly involved in the control of islet metabolism, beta-cell mass and islet neogenesis. These results, together with other previously reported, strongly indicate an important role of INGAP-PP, and possibly of INGAP, in the regulation of islet function and development.
Asunto(s)
Antígenos de Neoplasias/fisiología , Biomarcadores de Tumor/fisiología , Citocinas/biosíntesis , Regulación de la Expresión Génica , Islotes Pancreáticos/patología , Lectinas Tipo C/fisiología , Fragmentos de Péptidos/biosíntesis , Animales , Antígenos de Neoplasias/química , Biomarcadores de Tumor/química , Células Cultivadas , ADN Complementario/metabolismo , Glucosa/metabolismo , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Lectinas Tipo C/química , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Asociadas a Pancreatitis , Canales de Potasio/química , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Some ligands of pattern recognition receptors (PRR) are present on tumour cells. The role of PRR in signalling for cytokine and reactive oxygen intermediates (ROI) production by monocytes and monocyte-derived macrophages (MDM) stimulated with tumour cells was studied. MATERIALS AND METHODS: Monocytes/MDM were pretreated with PRR ligands or anti-PRR monoclonal antibodies (mAbs) and stimulated with tumour cells. Cytokine secretion was measured by enzyme-linked immunoassay (ELISA) and ROI production by luminol-dependent chemiluminescence (CL). RESULTS: The ligands of scavenger receptor A (SR-A): (fucoidan, polyguanylic acid (polyG) and modified low density lipoproteins (LDL)) and B (SR-B) (native and modified LDL, phosphatidylserine (PdS)) and of mannose receptor (MR) (mannan), induced tumour necrosis factor alpha (TNF) and ROI (except LDL) release by monocytes. Production of TNF and interleukin-10 (IL-10) by MDM was stimulated by SR-A ligands and mannan. Tumour cell-induced TNF and IL-10 production by monocytes, but not MDM, was diminished by fucoidan and polyG, while ROI release was reduced by MR and SR-A ligands. Supplementation of tumour cells with modified LDL and PdS enhanced their stimulatory capacity. TNF and ROI release by tumour cells-stimulated monocytes was inhibited by anti-CD36 and anti-MR (clone PAM-1) mAbs. CONCLUSION: SR and MR may be involved to different extents in the induction of cytokines and ROI production by monocytes, but not MDM, stimulated with tumour cells.
Asunto(s)
Citocinas/biosíntesis , Lectinas Tipo C/fisiología , Macrófagos/metabolismo , Lectinas de Unión a Manosa/fisiología , Monocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Superficie Celular/fisiología , Receptores Inmunológicos/fisiología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Anticuerpos Monoclonales/farmacología , Antígenos CD36/inmunología , Comunicación Celular/fisiología , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Lectinas Tipo C/inmunología , Lectinas Tipo C/metabolismo , Ligandos , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacología , Macrófagos/citología , Macrófagos/inmunología , Receptor de Manosa , Lectinas de Unión a Manosa/inmunología , Lectinas de Unión a Manosa/metabolismo , Monocitos/citología , Monocitos/inmunología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Fosfatidilserinas/metabolismo , Fosfatidilserinas/farmacología , Receptores de Superficie Celular/inmunología , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/inmunología , Receptores Inmunológicos/metabolismo , Receptores Depuradores , Receptores Depuradores de Clase A , Receptores Depuradores de Clase B , Transducción de SeñalRESUMEN
An increasing number of C-type lectin receptors are being discovered on dendritic cells, but their signaling abilities and underlying mechanisms require further definition. Among these, dendritic cell immunoreceptor (DCIR) induces negative signals through an inhibitory immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail. Here we identify a novel C-type lectin receptor, dendritic cell immunoactivating receptor (DCAR), whose extracellular lectin domain is highly homologous to that of DCIR. DCAR is expressed similarly in tissues to DCIR, but its short cytoplasmic portion lacks signaling motifs like ITIM. However, a positively charged arginine residue is present in the transmembrane region of the DCAR, which may explain its association with Fc receptor gamma chain and its stable expression on the cell surface. Furthermore, cross-linking of DCAR in the presence of gamma chain activates calcium mobilization and tyrosine phosphorylation of cellular proteins. These signals are mediated by the immunoreceptor tyrosine-based activating motif (ITAM) of the gamma chain. Thus, DCAR is closely related to DCIR, but it introduces activating signals into antigen-presenting cells through its physical and functional association with ITAM-bearing gamma chain. The identification of this activating immunoreceptor provides an example of signaling via a dendritic cell-expressed C-type lectin receptor.
Asunto(s)
Lectinas Tipo C/metabolismo , Lectinas Tipo C/fisiología , Glicoproteínas de Membrana , Receptores de IgG/química , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/fisiología , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Western Blotting , Calcio/metabolismo , Línea Celular , Células Cultivadas , Clonación Molecular , Reactivos de Enlaces Cruzados/farmacología , Citoplasma/metabolismo , ADN Complementario/metabolismo , Vectores Genéticos , Humanos , Lectinas/metabolismo , Lectinas Tipo C/química , Ratones , Ratones Endogámicos BALB C , Modelos Genéticos , Datos de Secuencia Molecular , Fosforilación , Pruebas de Precipitina , Estructura Terciaria de Proteína , ARN Mensajero/metabolismo , Receptores Inmunológicos/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Transducción de Señal , Espectrometría de Fluorescencia , Distribución Tisular , Tirosina/metabolismoRESUMEN
Hepatitis C virus (HCV) infects nearly 3% of the population of the world and is a major cause of liver disease. However, the mechanism whereby the virus targets the liver for infection remains unknown, because none of the putative cellular receptors for HCV are both expressed specifically in the liver and capable of binding HCV envelope glycoproteins. Liver/lymph node-specific intercellular adhesion molecule-3-grabbing integrin (L-SIGN) is a calcium-dependent lectin expressed on endothelial cells of liver and lymph nodes. Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), a homologous molecule expressed on dendritic cells, binds HIV and promotes infection. By using a virus-binding assay, we demonstrate that L-SIGN and DC-SIGN specifically bind naturally occurring HCV present in the sera of infected individuals. Further studies demonstrate that binding is mediated by the HCV envelope glycoprotein E2 and is blocked by specific inhibitors, including mannan, calcium chelators, and Abs to the lectin domain of the SIGN molecules. Thus, L-SIGN represents a liver-specific receptor for HCV, and L-SIGN and DC-SIGN may play important roles in HCV infection and immunity.
Asunto(s)
Moléculas de Adhesión Celular/fisiología , Hepacivirus/patogenicidad , Hepatitis C/virología , Lectinas Tipo C/fisiología , Hígado/virología , Receptores de Superficie Celular/fisiología , Receptores Virales/fisiología , Secuencia de Bases , Sitios de Unión , Moléculas de Adhesión Celular/genética , ADN Complementario/genética , ADN Viral/genética , Células HeLa , Hepacivirus/genética , Hepacivirus/fisiología , Humanos , Técnicas In Vitro , Lectinas Tipo C/genética , ARN Viral/genética , Receptores de Superficie Celular/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/fisiologíaRESUMEN
We have characterized the rat NK receptors NKR-P1A and -P1B. A cDNA library was constructed from the rat NK cell line, RNK-16. Using the pMX retroviral cloning system, the library was expressed in the human NK cell line, YTSeco, and cells staining with the anti-rat mAb 10/78 identified, FACS sorted and cloned. Two genes, corresponding to rat NK receptors NKR-P1A and -P1B, were identified. YTSeco clones expressing either NKR-P1A or -P1B were functionally tested using (51)Cr-release redirected lysis assays and calcium flux experiments. This demonstrated that NKR-P1A functions as an activation receptor, as previously shown, and that NKR-P1B functions as an inhibitory receptor, as predicted by the presence of an immunoreceptor tyrosine-based inhibition motif. Although annotated as NKR-P1A specific, we found that mAb 10/78 stained YTSeco clones expressing NKR-P1A or -P1B equally well, as did the mAb 3.2.3 used for the original cloning of rat NKR-P1A.