RESUMEN
Unlike mammals, the CNS of the medicinal leech can regenerate damaged neurites, thus restoring neural functions after lesion. We previously demonstrated that the injured leech nerve cord is able to mount an immune response promoting the regenerative processes. Indeed neurons and microglia express sensing receptors like Hm-TLR1, a leech TLR ortholog, associated with chemokine release in response to a septic challenge or lesion. To gain insights into the TLR signaling pathways involved during these neuroimmune responses, members of the MyD88 family were investigated. In the present study, we report the characterization of Hm-MyD88 and Hm-SARM. The expression of their encoding gene was strongly regulated in leech CNS not only upon immune challenge but also during CNS repair, suggesting their involvement in both processes. This work also showed for the first time that differentiated neurons of the CNS could respond to LPS through a MyD88-dependent signalling pathway, while in mammals, studies describing the direct effect of LPS on neurons and the outcomes of such treatment are scarce and controversial. In the present study, we established that this PAMP induced the relocalization of Hm-MyD88 in isolated neurons.
Asunto(s)
Proteínas del Citoesqueleto/metabolismo , Hirudo medicinalis/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Secuencia de Aminoácidos , Animales , Sistema Nervioso Central/metabolismo , Proteínas del Citoesqueleto/clasificación , Proteínas del Citoesqueleto/genética , Humanos , Lipopolisacáridos/toxicidad , Microglía/metabolismo , Datos de Secuencia Molecular , Factor 88 de Diferenciación Mieloide/clasificación , Factor 88 de Diferenciación Mieloide/genética , Regeneración Nerviosa , Neuronas/metabolismo , Alineación de Secuencia , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 1/genética , Receptor Toll-Like 1/metabolismoRESUMEN
The management of cerebral perfusion pressure (CPP) is the one of the main preoccupation for the care of paediatric traumatic brain injury (TBI). The physiology of cerebral autoregulation, CO2 vasoreactivity, cerebral metabolism changes with age as well as the brain compliance. Low CPP leads to high morbidity and mortality in pediatric TBI. The recent guidelines for the management of CPP for the paediatric TBI indicate a CPP threshold 40-50 mmHg (infants for the lower and adolescent for the upper). But we must consider the importance of age-related differences in the arterial pressure and CPP. The best CPP is the one that allows to avoid cerebral ischaemia and oedema. In this way, the adaptation of optimal CPP must be individual. To assess this objective, interesting tools are available. Transcranial Doppler can be used to determine the best level of CPP. Other indicators can predict the impairment of autoregulation like pressure reactivity index (PRx) taking into consideration the respective changes in ICP and CPP. Measurement of brain tissue oxygen partial pressure is an other tool that can be used to determine the optimal CPP.
Asunto(s)
Lesiones Encefálicas/fisiopatología , Encéfalo/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Adolescente , Adulto , Presión Sanguínea , Lesiones Encefálicas/diagnóstico , Arterias Cerebrales/fisiopatología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Presión Intracraneal/fisiología , Masculino , Perfusión , Valores de ReferenciaRESUMEN
The electrophoretic mobilities of separated "null" lymphocytes and of null and T cells bearing receptors for the fragment of immunoglobulins (Fc) portion of IgG have been studied in normal human blood. The data have been compared with those of other circulating subsets and with more conventional marker techniques. A large proportion of B cells was removed by nylon wool adherence. Further purification of the effluent cells separated 3 non-B populations using the property of sheep's red blood cells to form 2 types of rosettes with T cells on the basis of their relative affinity: "active" rosettes, and low affinity E-rosettes. A population of "null" cells was obtained which was effluent of the nylon wool column and non rosette-forming cells with SRBC (E-RFC). The average purity of this population was 85%; it was found to contain an increased proportion of rosette-forming cells with IgG coated erythrocytes (EA-IgG RFC) (41.3 +/- 10.4% vs. 11.9 +/- 3.8% in the total population) and exhibited high spontaneous incorporation of thymidine but low response to mitogens. The "null" cell population and its erythrocyte-antibody complex-rosette forming cells (EA-RFC) exhibited a defined electrophoretic mobility, centered between 1.05 and 1.15 micrometer. sec-1. v-1. cm in NaCl 0.145 M. The T populations, defined as ERFC, possessed different electrophoretic mobilities, and contained different proportions of Fc gamma receptor-bearing cells. Possessing an e. m. generally greater than 1.15 micrometer. sec-1. v-1. cm., high affinity "active" rosettes did not appear to contain EA-RFC, while the low affinity ERFC contained 18% (8 to 33) EA (IgG) RFC, and had an e.m. comprised between 1.00 and 1.15 micrometer. sec-1. v-1. cm. The presence of antibody-dependent cellular cytotoxicity was found to correlate with EA-RFC: mainly in EA-RFC of the "null" cells, but also to a lesser extent in EA-RFC of the low affinity ERFC. In normal human blood, these non-B Fc gamma receptor bearing cells appeared to possess a comparable electrophoretic mobility centered between 1.05 and 1.15 micrometer. sec-1. v-1. cm. in the "null" and low affinity ERFC subsets.
Asunto(s)
Linfocitos/citología , Receptores Fc , Adulto , Animales , Citotoxicidad Celular Dependiente de Anticuerpos , Linfocitos B/citología , Separación Celular , Electroforesis , Humanos , Ratones , Formación de Roseta , Linfocitos T/citologíaRESUMEN
Few data are available on the blood lymphocyte response to revaccination in man. The anamnestic response to tetanus toxoid challenge was evaluated by a variety of techniques during the first week after revaccination. Out of twenty subjects used, eight were evaluated before and 5 days after the injections (days 1--8). Analytical cell electrophoresis showed important variation in the B and two T lymphocyte populations. The B cell percentages, assessed by EAC-rosettes and electrophoretic mobility, were found to decrease by days 2 and 3, and return to former levels by day 8, when a rise in specific antibodies was detected. A similar response was found in the T1 population generally considered to be composed of low affinity E-rosette-forming cells. Conversely, a significant increase (50--100%) in circulating T2 lymphocytes (active rosette-forming cells) was found by days 2 and 3, followed by a rapid decrease of these 'differenciated' cells. The increase in the T2 lymphocytes appeared earlier in skin test positive subjects. These changes were correlated with E-rosettes, mitogen stimulation, peripheral leucocyte migration inhibition and transformation in the presence of the antigen. EA-IgG rosettes and ADCC varied similarly. These results may indicate a significant non-specific cell mobilization following revaccination.
Asunto(s)
Inmunización Secundaria , Linfocitos/inmunología , Toxoide Tetánico/inmunología , Citotoxicidad Celular Dependiente de Anticuerpos , Inhibición de Migración Celular , Electroforesis , Humanos , Recuento de Leucocitos , Leucocitos/inmunología , Activación de Linfocitos , Formación de Roseta , Pruebas CutáneasRESUMEN
Cell surface charge, assessed by the analytical electrophoresis of fresh and cryopreserved human peripheral blood lymphoctes, is changed in any perceivable manner by freezing and thawing. This was confirmed by different membrane markers (E, EA and EAC rosettes).
Asunto(s)
Linfocitos , Adulto , Conservación de la Sangre , Supervivencia Celular , Electroforesis , Congelación , Humanos , Linfocitos/inmunología , Receptores de Antígenos de Linfocitos B , Formación de RosetaRESUMEN
Clinical findings in cancer patients and experimental results after separation of active rosettes-forming cells are compatible with the hypothesis that the lymphocytes which do form active rosettes are those whose electrophoretic mobility is about 1.20 micron. sec-1v.-1.cm.
Asunto(s)
Técnicas Inmunológicas , Neoplasias/inmunología , Linfocitos T/inmunología , Humanos , Inmunoelectroforesis , Linfocitos T/análisisRESUMEN
The electrophoretic mobility of circulating lymphocytes has been studied in normal human subjects after immunization by tetanus toxoid. The mean migration speed was shown to increase, particularly two and three days after secondary immunization. This increase appeared to be due to the elevation of percentage of T cells migrating at 1.20 and 1.35 micrometer. sec.-1v.-1 cm. (active rosettes-forming cells), with a decrease of the percentage of B cells and T lymphocytes migrating at 1.10 micrometer. sec.-1v.-1 cm. The return to the anterior status was observed between day 4 and 8 after immunization.