RESUMO
Performance status (PS) frequently improves occurs in cancer patients who have been infused with their own lymphokine-activated killer T cells (LAK-T). In the present study, a culture supernatant of LAK-T (LAK-T sup) administered to 8-week-old rats caused neurogenesis as evidenced by increased 5-ethynyl-2'-deoxyuridine staining of brain tissues. Intravenous injection of granulocyte-macrophage colony stimulating factor (GM-CSF), a major cytokine in LAK-T sup, had a similar effect. Furthermore, LAK-T sup induced Ca(++) increase in rat hippocampal brain slices that was detected in neuronal cells by emission of Fluo-8 NW at 520 nm. The same effect was observed with an rGM-CSF solution. GM-CSF may activate neuronal cells by stimulating the glial cells that surround and attach to them. If so, GM-CSF and LAK-T sup may improve the motor neurons of patients with amyotrophic lateral sclerosis. The neurogenerative effect of GM-CSF in LAK-T sup may also help improve brain function in aged adults including those with dementia such as Alzheimer's disease.
Assuntos
Anticorpos Monoclonais/farmacologia , Interleucina-2/farmacologia , Células Matadoras Ativadas por Linfocina/imunologia , Neurônios/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Adulto , Doença de Alzheimer/terapia , Esclerose Lateral Amiotrófica/terapia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/patologia , Proliferação de Células/fisiologia , Citocinas/imunologia , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Imunoterapia Adotiva/métodos , Interleucina-2/imunologia , Células Matadoras Ativadas por Linfocina/citologia , Células Matadoras Ativadas por Linfocina/efeitos dos fármacos , Células Matadoras Ativadas por Linfocina/transplante , Masculino , Neurogênese/imunologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Linfócitos T Citotóxicos/imunologia , Regulação para CimaRESUMO
Thrombin-activatable fibrinolysis inhibitor (TAFI) is an anaphylatoxin-inactivating enzyme generated by proteolytic cleavage of its zymogen, and is the same enzyme as that first designated by our group as procarboxypeptidase R (proCPR). TAFI in plasma is presumed to influence vascular disease in its role as a fibrinolysis inhibitor. The activity of TAFI is strongly influenced by genetic polymorphism, especially at amino acids Thr/Ala-147 and Thr/Ile-325. In this study, we analyzed 202 healthy controls who were not on any medication, had no unusual medical history and whose blood data were normal. In a previous report, we established an enzyme-linked immunosorbent assay (ELISA) specific for non-activated TAFI (proCPR), and investigated levels of unactivated TAFI as an estimate of anti-fibrinolytic capacity. In this study, we determined normal Japanese TAFI levels for each age, sex, and genetic polymorphism of Thr/Ala-147 and Thr/Ile-325, and also showed that the TAFI level in young adult women is lower than in aged women.