RESUMEN
NKR-P1A protein has been implicated in the triggering of NK-mediated natural killing contributing to target cell recognition by NK cells. The aim of the present work was to assess whether NKR-P1A receptor triggering also induced arachidonic acid (AA) generation and to determine the possible role of this event on granule release and cytotoxicity. We demonstrated that activation of fresh peripheral blood rat NK cells by cross-linking with the anti-NKR-P1A 3.2.3 mAb induced calcium-dependent AA release, which is due to the activation of cytosolic phospholipase A2 (cPLA2), secretory phospholipase A2 (sPLA2), and diacylglycerol/monoacylglycerol lipase. We also documented the presence of a type II sPLA2 activity in the supernatant fluids from NKR-P1A-activated rat NK cells, suggesting that AA and lysophospholipids could be mobilized from the outside of the cell. The involvement of AA-generating enzymes in NKR-P1A-induced cytotoxic functions was also investigated. Treatment of effector cells with arachidonyl trifluoromethylketone, a cPLA2 inhibitor; p-bromophenacylbromide, a sPLA2 inhibitor; or RHC80267, a diacylglycerol lipase inhibitor, led to a partial inhibition of the redirected lysis against P815 target cells as well the granule content release induced by NKR-P1A cross-linking. A complete abolishment of these events was observed when the cells were simultaneously incubated with all three inhibitors. Taken together, our results support a crucial role for the arachidonate-generating enzymes in the induction of lytic activity of NK cells directly or by leading to generation of additional mediators that can play a role in the context of NK cell activation and cytotoxic functions.
Asunto(s)
Antígenos de Superficie/metabolismo , Ácido Araquidónico/metabolismo , Gránulos Citoplasmáticos/metabolismo , Células Asesinas Naturales/metabolismo , Lectinas Tipo C , Animales , Antígenos de Superficie/inmunología , Células Cultivadas , Gránulos Citoplasmáticos/ultraestructura , Citotoxicidad Inmunológica , Exocitosis/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/ultraestructura , Activación de Linfocitos , Subfamilia B de Receptores Similares a Lectina de Células NK , Fosfolipasas A/metabolismo , Fosfolipasas A2 , Ratas , Ratas Wistar , Receptores Inmunológicos/inmunología , Receptores Inmunológicos/metabolismoRESUMEN
This study concerns 20 patients with cerebrovascular disease in the course of oral contraception with estrogens/progestins. The assumption of oral contraceptives appears to be related to the cerebrovascular manifestations, which could be caused by alterations of the blood vessel walls or of the coagulative process induced by estrogens/progestins. The thrombogenic action of these substances could be enhanced by preexisting conditions such as protein C or protein S deficiency.
Asunto(s)
Trastornos Cerebrovasculares/inducido químicamente , Anticonceptivos Orales Combinados/efectos adversos , Adulto , Síndrome Antifosfolípido/complicaciones , Trastornos Cerebrovasculares/etiología , Trastornos Cerebrovasculares/fisiopatología , Susceptibilidad a Enfermedades , Femenino , Humanos , Persona de Mediana Edad , Trastornos Migrañosos/complicaciones , Prolapso de la Válvula Mitral/complicaciones , Deficiencia de Proteína C , FumarRESUMEN
In the study of potential generators the dipole localization method is often used. The "equivalent dipole" represents the resultant of all the neurobiological processes (excitatory and inhibitory post-synaptic potentials, action potentials) that concur to generate the evoked potentials. According to the dipole's distance from the active electrode, "near-field" and "far-field" potentials will be recorded, with differences in the spatiotemporal distribution to the skin. The main hypotheses about the generators of standard components of somatosensory evoked potentials (SEP) from median and posterior tibial nerve, visual evoked potentials (VEP), auditory brainstem evoked potentials (BAEP) and P300, are analyzed.
Asunto(s)
Potenciales Evocados Auditivos/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Potenciales Evocados Visuales/fisiología , Tronco Encefálico/fisiología , HumanosRESUMEN
Clarification of the extent and mechanisms of damage to the central nervous system in diabetes is a frontier of current neurological research. Our aim was to obtain ample electrophysiological documentation of possible neurological abnormalities in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients with a short duration of disease and without overt complications, taking into account metabolic control. Group 1 comprised 11 IDDM patients, and group 2 included 14 NIDDM patients treated with diet alone; the duration of disease was less than 4 yr, and no concomitant clinical complications were present. Age- and sex-matched normal subjects formed groups 3 and 4. Pattern visual evoked potentials (VEP), brain stem auditory evoked potentials (BAEP), and somatosensory evoked potentials (SEP; after the stimulation of both median and tibial nerves) were recorded in all subjects, and metabolic control was evaluated in terms of glycemia and glycosylated hemoglobin. In group 1, significant abnormalities were found in the latency values of VEP, median SEP, and tibial SEP compared with control subjects. Similar latency abnormalities were shown in group 2 for VEP, median SEP, and tibial SEP values and for wave I latency of BAEP. Glycosylated hemoglobin values were correlated with BAEP and SEP abnormalities in many patients in both groups. Furthermore, in group 2, glycemic values correlated with SEP abnormalities. We therefore conclude that neurophysiological abnormalities are present at different levels in IDDM and NIDDM patients only a few years after clinical diagnosis and before the appearance of overt complications, and these abnormalities seem to be correlated with metabolic control status.
Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/diagnóstico , Potenciales Evocados Auditivos , Potenciales Evocados Somatosensoriales , Potenciales Evocados Visuales , Adulto , Glucemia/análisis , Tronco Encefálico/fisiopatología , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/prevención & control , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
The Authors have examined 20 subjects affected by "possible" multiple sclerosis by means of a multimodal (VEP, BAEP, SEP) electrophysiologically evaluation longitudinally conducted during a time period of 1 year. The electrophysiological data obtained are related to the clinical picture, the disease's evolution, and to the adopted pharmacological therapy, in order to attempt a more precise diagnostic and prognostic assessment of these patients.