RESUMEN
In this study, we report that an acute phase reactant, serum amyloid A (SAA), strongly inhibits dendritic cell differentiation induced by GM-CSF plus IL-4. SAA markedly decreased the expression of MHCII and CD11c. Moreover, SAA decreased cell surface GM-CSF receptor expression. SAA also decreased the expression of PU.1 and C/EBPα, which play roles in the expression of GM-CSF receptor. This inhibitory response by SAA is partly mediated by the well-known SAA receptors, Toll-like receptor 2 and formyl peptide receptor 2. Taken together, we suggest a novel insight into the inhibitory role of SAA in dendritic cell differentiation.
Asunto(s)
Células Dendríticas , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Interleucina-4 , Receptores de Formil Péptido , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos , Proteína Amiloide A Sérica , Receptores Toll-LikeRESUMEN
Wnt5a is a ligand that activates the noncanonical Wnt signaling pathways (beta-catenin-independent pathways). Human neutrophils expressed several Wnt5a receptors, such as Frizzled 2, 5 and 8. Stimulation of human neutrophils with Wnt5a caused chemotactic migration and the production of two important chemokines, CXCL8 and CCL2. CCL2 production by Wnt5a was mediated by a pertussis toxin-sensitive G-protein-dependent pathway. Wnt5a also stimulated the phosphorylation of three mitogen-activated protein kinases (MAPKs: ERK, p38 MAPK and JNK) and Akt. Inhibition of ERK, p38 MAPK or JNK by specific inhibitors induced a dramatic reduction in Wnt5a-induced CCL2 production. Supernatant collected from lipopolysaccharide-stimulated macrophages induced neutrophil chemotaxis, which was significantly inhibited by anti-Wnt5a antibody. Our results suggested that Wnt5a may contribute to neutrophil recruitment, mediating the inflammation response.
Asunto(s)
Animales , Humanos , Ratones , Factor de Transcripción Activador 2/metabolismo , Separación Celular , Quimiocinas/biosíntesis , Quimiotaxis/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas de Unión al GTP/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , FN-kappa B/metabolismo , Neutrófilos/citología , Toxina del Pertussis/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Wnt/metabolismo , Fosfolipasas de Tipo C/metabolismo , Proteínas Wnt/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Neutrophils play a key role in innate immunity, and the identification of new stimuli that stimulate neutrophil activity is a very important issue. In this study, we identified three novel peptides by screening a synthetic hexapeptide combinatorial library. The identified peptides GMMWAI, MMHWAM, and MMHWFM caused an increase in intracellular Ca2+ in a concentration-dependent manner via phospholipase C activity in human neutrophils. The three peptides acted specifically on neutrophils and monocytes and not on other non-leukocytic cells. As a physiological characteristic of the peptides, we observed that the three peptides induced chemotactic migration of neutrophils as well as stimulated superoxide anion production. Studying receptor specificity, we observed that two of the peptides (GMMWAI and MMHWFM) acted on formyl peptide receptor (FPR)1 while the other peptide (MMHWAM) acted on FPR2. Since the three novel peptides were specific agonists for FPR1 or FPR2, they might be useful tools to study FPR1- or FPR2-mediated immune response and signaling.
Asunto(s)
Animales , Humanos , Ratones , Ratas , Calcio/metabolismo , Línea Celular , Células Cultivadas , Quimiotaxis de Leucocito/efectos de los fármacos , Células 3T3 NIH , Neutrófilos/citología , Células PC12 , Péptidos/farmacología , Receptores de Formil Péptido/agonistasRESUMEN
PURPOSE: Cystatin C has been proposed for the assessment of glomerular filtration rate, being more accurate than creatinine determination. We measured serum cystatin C concentrations in the pediatric population, and analysed the correlation between cystatin C and glomerular filtration rate. METHODS: Cystatin C and creatinine were measured by the particle enhanced nephelometric immunoassay and Jaff'e method, respectively, in 276 children and adolescents without evidence of kidney disease. The glomerular filtration rate was estimated by Schwartz's formula. RESULTS: The mean serum cystatin C concentration was significantly higher in infants under the age of 12 months than in older population. There was a negative correlation between cystatin C and age under 12 months, but not a significant change of cystatin C with age in children older than 12 months For children older than 12 months, the reference range of cystatin C was 0.46-1.05 mg/L. On the other hand, there was a positive correlation between creatinine and age in the whole population. We also observed a positive correlation between estimated glomerular filtration rate and 1/ cystatin C. CONCLUSION: The measurement of cystatin C is more practical than creatinine for estimating glomerular filtration rate in the pediatric population.
Asunto(s)
Adolescente , Niño , Humanos , Lactante , Creatinina , Cistatina C , Tasa de Filtración Glomerular , Mano , Inmunoensayo , Enfermedades Renales , Valores de ReferenciaRESUMEN
Congenital hypopituitarism is a rare disorder with absence or reduction of hormones produced by the pituitary gland. The clinical manifestations are hypoglycemia, prolonged jaundice, hyponatremia, micropenis, underdeveloped clitoris, lethargy, convulsion, pallor, cyanosis, apnea, hypotension, temperature instability etc. in neonates and growth failure, delayed or absent puberty in older infants and children. We experienced a case of congenital hypopituitarism who was a 20-year-old male patient with short stature and delayed puberty. Combined pituitary function test revealed panhypopituitarism and magnetic resonance imaging of brain showed anterior pituitary aplasia and ectopic posterior pituitary gland.
Asunto(s)
Adolescente , Niño , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Adulto Joven , Apnea , Encéfalo , Clítoris , Cianosis , Hipoglucemia , Hiponatremia , Hipopituitarismo , Hipotensión , Ictericia , Letargia , Imagen por Resonancia Magnética , Palidez , Pruebas de Función Hipofisaria , Hipófisis , Neurohipófisis , Pubertad , Pubertad Tardía , ConvulsionesRESUMEN
Congenital hypopituitarism is a rare disorder with absence or reduction of hormones produced by the pituitary gland. The clinical manifestations are hypoglycemia, prolonged jaundice, hyponatremia, micropenis, underdeveloped clitoris, lethargy, convulsion, pallor, cyanosis, apnea, hypotension, temperature instability etc. in neonates and growth failure, delayed or absent puberty in older infants and children. We experienced a case of congenital hypopituitarism who was a 20-year-old male patient with short stature and delayed puberty. Combined pituitary function test revealed panhypopituitarism and magnetic resonance imaging of brain showed anterior pituitary aplasia and ectopic posterior pituitary gland.