RESUMEN
Multidrug resistance-1 (MDR-1) is characterized by overfunction of P-glycoprotein (P-gp), a pump molecule that decreases intracellular drug concentration by effluxing them from the intracellular space. Broad ranges of structurally unrelated compounds are transported by P-gp, including antineoplastic agents, HIV protease inhibitors, prednisone, gold salts, methotrexate, colchicine as well as several antibiotics. In contrast, many other compounds such as calcium channel blockers (verapamil) and immunosupressors (cyclosporine-A) are able to inhibit P-gp function. The P-gp role in therapeutic failures has been extensively studied in cancer; however, there is little information regarding MDR-1 phenotype in autoimmune disorders. It has been reported that an increased number of lymphocytes are able to extrude P-gp substrates in rheumatoid arthritis, immune thrombocytopenic purpura and systemic lupus erythematosus, the patients with poor response to treatment being the ones that exhibit the highest values. This may be due, at least in part, to a simultaneous long-term usage of several drugs that induce P-gp function. Since abnormally activated cell compartments characterize autoimmune diseases, it is possible that those cells are the ones that exhibit drug resistance. The study of drug resistance mechanisms in autoimmunity may be helpful for the optimization of the current therapeutic schemes through their combination with low doses of P-gp inhibitors.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Artritis Reumatoide/metabolismo , Resistencia a Múltiples Medicamentos/inmunología , Lupus Eritematoso Sistémico/metabolismo , Linfocitos/metabolismo , Púrpura Trombocitopénica Idiopática/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/inmunología , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Bloqueadores de los Canales de Calcio/metabolismo , Bloqueadores de los Canales de Calcio/uso terapéutico , Inhibidores de la Proteasa del VIH/metabolismo , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Inmunosupresores/metabolismo , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Activación de Linfocitos/inmunología , Activación de Linfocitos/fisiología , Linfocitos/inmunología , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/inmunologíaRESUMEN
Autoantibodies directed to beta2 glycoprotein I (a beta 2 GPI) are frequently found in patients with antiphospholipid antibodies (aPL). They are more strongly associated with clinical manifestations of the antiphospholipid syndrome then a PL. It has been shown that beta2 GPI and C4b bibding protein (C4bBP) share certain homology. In a previous study we have shown that anticardiolipin antibodies were associated with a plasma decrease of C4bBP. The aim of the present study was to evaluate in 131 patients with a PL whether the decrease in C4bBP is related to the presence of abeta2 GPI. Lower C4bBP levels (mean +- SD) in the group of patients having abeta2 GPI (n=57) were observed when compared with the normal group (n=44), (74.3 porciento +-28.1 vs 94.6 porciento +-20.9,p<0.005).This difference was more significant consideing the IgG isotype. The group of patients with positive abeta2GPI-igG (n=41) had lower values of C4bBP (70.1 porciento +- 26.8) than both the normal group (p<0.005) and the group of patients with negative abeta2 IgG (n=90, 86.0 porciento +- 30.5 porciento, p<0.05). C4bBP deficiency (level <70 porciento) was also morefrequent in the group abeta 2GPI-IgG (+) (63.4 porciento) then in the group abeta2GPI-IgG 8-) (34.4 porciento, p<0.005). Moreover, patients with a PL and previews venous thrombosis (n=32) showed lower C4bBP values (75.1 porciento +- 27.9) compared with the normal group (p<0.05). As this time, the mechanisms responsibles for the C4bBP decrease are not known. Our findings on the close relationship between abnormalitiesin the C4bBP/protein S system and the presence of abeta2GPI could explain the major thrombotic risk in patients havingthese autoantibodies
Asunto(s)
Anticuerpos Antifosfolípidos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/clasificación , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/inmunologíaRESUMEN
Objetivo: En este artículo se revisan algunos aspectos relevantes de la fagocitosis no opsónica de microorganismos intracelulares con especial énfasis en Histoplasma capsulatum, considerando que la participación de los mecanismos no opsónicos influyen en el destino final de los microorganismos dentro de los fagocitos. Introducción: Numerosos microorganismos intracelulares invaden y sobreviven en el interior de las células fagocíticas gracias a los medios utilizados para su internalización así como a la presencia de moléculas de superficie o productos metabólicos que neutralizan o inhiben los mecanismos microbicidas propios de los fagocitos del huésped. Participación de moléculas glicosiladas, de integrinas, y de otras moléculas, en la invasión de microorganismos al macrófago: La internalización de los microorganismos a través de los receptores independientes de opsoninas de los macrófagos generalmente facilita a la invasión de éstos, ya que algunos receptores no activan el metabolismo oxidativo, de ahí que el reconocimiento, entre la célula a ser infectada y el microorganismo, mediaso por carbohidratos y estructuras tipo lectinas constituye uno de los mecanismos de invasión más exitosos. Conclusión: El conocer estas alternativas de invasión favorecería entender mejor la patogénesis de muchas enfermedades intracelulares que representan importantes problemas de salud, como la histoplasmosis, la tuberculosis y la leishmaniasis, entre otras
Asunto(s)
Humanos , Animales , Activación de Macrófagos/inmunología , Antígenos de Histocompatibilidad Clase II , Mecanismos de Defensa , Histoplasma/aislamiento & purificación , Histoplasma/patogenicidad , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/inmunología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Fagocitosis , Interacciones Huésped-ParásitosRESUMEN
Autoantibodies directed to beta2 glycoprotein I (a beta 2 GPI) are frequently found in patients with antiphospholipid antibodies (aPL). They are more strongly associated with clinical manifestations of the antiphospholipid syndrome then a PL. It has been shown that beta2 GPI and C4b bibding protein (C4bBP) share certain homology. In a previous study we have shown that anticardiolipin antibodies were associated with a plasma decrease of C4bBP. The aim of the present study was to evaluate in 131 patients with a PL whether the decrease in C4bBP is related to the presence of abeta2 GPI. Lower C4bBP levels (mean +- SD) in the group of patients having abeta2 GPI (n=57) were observed when compared with the normal group (n=44), (74.3 porciento +-28.1 vs 94.6 porciento +-20.9,p<0.005).This difference was more significant consideing the IgG isotype. The group of patients with positive abeta2GPI-igG (n=41) had lower values of C4bBP (70.1 porciento +- 26.8) than both the normal group (p<0.005) and the group of patients with negative abeta2 IgG (n=90, 86.0 porciento +- 30.5 porciento, p<0.05). C4bBP deficiency (level <70 porciento) was also morefrequent in the group abeta 2GPI-IgG (+) (63.4 porciento) then in the group abeta2GPI-IgG 8-) (34.4 porciento, p<0.005). Moreover, patients with a PL and previews venous thrombosis (n=32) showed lower C4bBP values (75.1 porciento +- 27.9) compared with the normal group (p<0.05). As this time, the mechanisms responsibles for the C4bBP decrease are not known. Our findings on the close relationship between abnormalitiesin the C4bBP/protein S system and the presence of abeta2GPI could explain the major thrombotic risk in patients havingthese autoantibodies (AU)