RESUMEN
The urinary tract functions in close proximity to the outside environment, yet must remain free of microbial colonization to avoid disease. The mechanisms for establishing an antimicrobial barrier in this area are not completely understood. Here, we describe the production and function of the cathelicidin antimicrobial peptides LL-37, its precursor hCAP-18 and its ortholog CRAMP in epithelial cells of human and mouse urinary tract, respectively. Bacterial contact with epithelial cells resulted in rapid production and secretion of the respective peptides, and in humans LL-37/hCAP-18 was released into urine. Epithelium-derived cathelicidin substantially contributed to the protection of the urinary tract against infection, as shown using CRAMP-deficient and neutrophil-depleted mice. In addition, clinical E. coli strains that were more resistant to LL-37 caused more severe urinary tract infections than did susceptible strains. Thus, cathelicidin seems to be a key factor in mucosal immunity of the urinary tract.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/metabolismo , Infecciones por Escherichia coli/microbiología , Infecciones Urinarias/microbiología , Sistema Urinario/microbiología , Urotelio/microbiología , Animales , Antiinfecciosos/farmacología , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/orina , Niño , Farmacorresistencia Bacteriana , Células Epiteliales/citología , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/patología , Humanos , Inmunidad Mucosa , Corteza Renal/citología , Corteza Renal/metabolismo , Corteza Renal/microbiología , Corteza Renal/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Pruebas de Sensibilidad Microbiana , Neutrófilos/metabolismo , Sistema Urinario/efectos de los fármacos , Infecciones Urinarias/inmunología , Infecciones Urinarias/patología , Urotelio/citología , Urotelio/metabolismo , CatelicidinasRESUMEN
OBJECTIVE: Advanced oxidation protein products (AOPPs) represent dityrosine-containing cross-linked protein modifications formed mainly via myeloperoxidase reaction, supposed to accelerate the uremia-associated atherogenesis and renal fibrosis. DESIGN, SUBJECTS, AND MAIN OUTCOME MEASURES: In a cross-sectional study, we investigated the accumulation of AOPPs and advanced glycation end product (AGE)-specific fluorescence corrected for albumin in children and adolescents with chronic renal failure (CRF, n = 42), end-stage renal disease (ESRD, n = 12), kidney transplanted patients (Tx, n = 16), and age-matched healthy controls (n = 38). RESULTS: AOPP levels were 2.4-fold higher in the CRF and ESRD patients, and 1.6-fold higher in the transplanted subjects when compared with the controls (P < .001). In comparison with healthy controls, AGE levels rose 2-fold in the CRF, 7-fold in the ESRD, and 5-fold in the kidney transplanted children and adolescents, (P < .001). Patients with cardiovascular affliction presented with higher AGE levels than those without diagnosed cardiovascular disease (P < .02). In patients with stabilized renal function, AOPP and AGE levels did not change significantly during 12 months. CONCLUSION: Pattern of accumulation of AOPP and AGE in children and adolescents with chronic renal disease differs. Accelerated rise in AOPP levels in some children and adolescents in predialysis stage of chronic renal insufficiency, inadequate to deterioration of renal function, might require further attention.
Asunto(s)
Proteínas Sanguíneas/análisis , Productos Finales de Glicación Avanzada/sangre , Insuficiencia Renal Crónica/sangre , Adolescente , Adulto , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/complicaciones , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Trasplante de Riñón , Masculino , Estrés Oxidativo , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/cirugía , Albúmina Sérica/análisisRESUMEN
A novel approach to clinical-biochemical analysis of urine is presented in this work. Urine composition is defined graphically as a record of synchronous fluorescence spectra (SFS). The graphical standard has been made from SFS of urine samples from healthy children. Simple comparison of a standard record with that of an analyzed urine sample will immediately reveal changes in its composition. Reproducibility of the graphical definition is very high and it maintains its characteristic shape during repeated measurements over a span of 2 years. It is possible to elaborate patients' own standard for those with chronic illness. It differs from a normal course but it is characteristic for a given patient and it enables the clinician to monitor changes or the outcome of therapy at regular medical examinations. Application of this method for monitoring of urine composition for selected cases is a new alternative with several advantages. Analysis without any added reagents very quickly detects some illnesses near onset when they may be clinically asymptomatic and classical screening methods show negative results. Computerization of spectral measuring and filing the results enables to give a likely diagnosis or a deviation from standard. This method can also serve a doctor-clinician either to confirm or to exclude a concrete diagnosis.