RESUMEN
Formation of advanced glycation end products (AGEs) is accelerated in diabetic subjects along with hyperglycemia. Although several lines of evidence indicate that AGEs stimulate macrophages to secrete several cytokines and growth factors, little is known about the effect of AGEs on the primary function of macrophages, such as phagocytosis. On the other hand, impairment of the phagocytic function of monocytes/macrophages is suggested to contribute to the low resistance to infection in diabetic subjects. In the present study, we examined the effect of AGEs on the phagocytic function of macrophages. Using flow cytometric analysis of mouse resident peritoneal macrophages, we showed that AGEs suppress phagocytosis of fluorescent microspheres by cultured macrophages. In addition, experiments using streptozotocin-induced diabetic mice demonstrated a significant decrease in the phagocytic activity of resident peritoneal macrophages 12 weeks after induction of diabetes compared with age-matched control mice. The phagocytic activity of peritoneal macrophages correlated inversely with AGE content in the adjacent peritoneal tissue. Furthermore, reduced phagocytic activity of macrophages was associated with a reduction in intracellular ATP content. Because phagocytosis is an important component of the defense system, suppression of such activity by AGEs may explain, at least in part, the increased susceptibility of diabetic patients to infection.
Asunto(s)
Diabetes Mellitus Experimental/inmunología , Productos Finales de Glicación Avanzada/biosíntesis , Macrófagos Peritoneales/inmunología , Fagocitosis , Adenosina Trifosfato/metabolismo , Animales , Bovinos , Separación Celular , Inhibidores Enzimáticos/farmacología , Femenino , Citometría de Flujo , Indoles/farmacología , Maleimidas/farmacología , Ratones , Ratones Endogámicos BALB C , NG-Nitroarginina Metil Éster/farmacología , Norleucina/análogos & derivados , Norleucina/metabolismo , Proteína Quinasa C/antagonistas & inhibidores , Pirroles/metabolismoRESUMEN
We describe a 52-year-old male manifesting severe insulin resistance associated with hypereosinophilic syndrome (HES). Diabetes mellitus was initially well-controlled by an oral hypoglycemic agent, and thereafter by human insulin. Due to the progression of hypereosinophilia, hepatosplenomegaly and peripheral lymphoadenopathy, severe insulin resistance associated with diabetic ketoacidosis occurred repeatedly, despite intravenous administration of over 1,000 U per day of human insulin. A high plasma insulin-binding capacity as determined by Scatchard analysis was consistent with insulin antibody-mediated resistance. The diagnosis of HES was made due to the persistent elevation of eosinophil count and associated liver and cardiac damage. Glucocorticoid therapy successfully achieved both reducing clinical symptoms and improving glycemic control.
Asunto(s)
Complicaciones de la Diabetes , Síndrome Hipereosinofílico/complicaciones , Anticuerpos Insulínicos/inmunología , Resistencia a la Insulina/inmunología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/inmunología , Cetoacidosis Diabética/etiología , Cetoacidosis Diabética/inmunología , Humanos , Síndrome Hipereosinofílico/inmunología , Insulina/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
A 37-year-old female, who had been suffering from progressive systemic sclerosis (PSS) with long-term renal failure, was diagnosed as MPO-ANCA positive PSS in active stage. She had systemic scleroderma, normotensive renal failure and pulmonary fibrosis. Respiratory management and steroid therapy under the control of CVVH were done for her treatment. She developed hemolytic anemia and thrombocytopenia during the treatment. She was diagnosed as microangiopathic hemolytic anemia, and was treated with plasma exchange treatment. About eight weeks after her admission, she developed status epileptics. Cerebral computed tomography and lumbar puncture did not reveal any abnormal sign. The case reported herein is a MPO-ANCA positive PSS with normotensive renal failure. Generally, PSS rarely reveals neurological sign. This case suggests possibility of association between MPO-ANCA and systemic vasculitis in PSS.