RESUMEN
Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse transendothelial migration (RTM) into the arterial circulation after systemic stimulation of pattern-recognition receptors (PRRs). This process was dependent on expression of the chemokine receptor CCR7 and its ligand CCL19 by intimal myeloid cells. In mice infected with the intracellular pathogen Chlamydia muridarum, blood monocytes disseminated infection to the intima. Subsequent CCL19-CCR7-dependent RTM was critical for the clearance of intimal C. muridarum. This process was inhibited by hypercholesterolemia. Thus, RTM protects the normal arterial intima, and compromised RTM during atherogenesis might contribute to the intracellular retention of pathogens in atherosclerotic lesions.
Asunto(s)
Quimiocina CCL19/metabolismo , Chlamydia muridarum/inmunología , Células Mieloides/inmunología , Células Mieloides/metabolismo , Receptores CCR7/metabolismo , Migración Transendotelial y Transepitelial , Túnica Íntima/inmunología , Túnica Íntima/metabolismo , Animales , Antígeno CD11c/metabolismo , Infecciones por Chlamydia/inmunología , Infecciones por Chlamydia/metabolismo , Infecciones por Chlamydia/virología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Lipopolisacáridos/inmunología , Masculino , Ratones , Ratones Noqueados , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/microbiología , ARN Mensajero/genética , Transducción de Señal , Receptores Toll-Like/metabolismo , Túnica Íntima/microbiologíaRESUMEN
Integrins are adhesion molecules critical for the recruitment of leukocytes from blood into peripheral tissues. However, whether integrins are also involved in leukocyte exit from peripheral tissues via afferent lymphatics to the draining lymph node remains poorly understood. In this article, we show that adhesion by the collagen IV-binding integrin α1ß1 unexpectedly inhibited macrophage exit from inflamed skin. We monitored macrophages exiting mouse footpads using a newly developed in situ pulse labeling technique. Blockade of α1ß1 integrin or genetic deletion (Itga1(-/-)) increased macrophage exit efficiency. Chemotaxis assays through collagen IV showed more efficient migration of Itga1(-/-) macrophages relative to wild type. Given that macrophages are key orchestrators of inflammation, α1ß1 integrin adhesion may represent a mechanism for regulating inflammatory responses by controlling macrophage exit or persistence in inflamed tissues.
Asunto(s)
Inhibición de Migración Celular/inmunología , Mediadores de Inflamación/fisiología , Integrina alfa1beta1/fisiología , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/patología , Proteínas Adaptadoras Transductoras de Señales , Animales , Antígenos CD/biosíntesis , Antígenos CD/genética , Adhesión Celular/genética , Adhesión Celular/inmunología , Inhibición de Migración Celular/genética , Pie , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Mediadores de Inflamación/metabolismo , Cadenas alfa de Integrinas/biosíntesis , Cadenas alfa de Integrinas/deficiencia , Cadenas alfa de Integrinas/genética , Integrina alfa1beta1/biosíntesis , Integrina alfa1beta1/deficiencia , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/patología , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/deficiencia , Proteínas del Tejido Nervioso/fisiologíaRESUMEN
An 82-year-old woman underwent complicated cataract surgery with subsequent endophthalmitis. She presented with a unique purulent collection with ciliary body involvement and Klebsiella pneumoniae was grown on culture. Klebsiella is a rare cause of endophthalmitis and ciliary body involvement has not previously been reported.
Asunto(s)
Extracción de Catarata/efectos adversos , Endoftalmitis/microbiología , Infecciones Bacterianas del Ojo/microbiología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/aislamiento & purificación , Infección de la Herida Quirúrgica/microbiología , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Cuerpo Ciliar/microbiología , Cuerpo Ciliar/patología , Endoftalmitis/diagnóstico , Infecciones Bacterianas del Ojo/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Inyecciones , Infecciones por Klebsiella/diagnóstico , Infección de la Herida Quirúrgica/diagnóstico , Vitrectomía , Cuerpo VítreoRESUMEN
Models of inflammatory and immune diseases are extensively studied in mice with engineered genetic mutations, and tracking the recruitment of blood leukocytes into tissues is an important component of these studies. A direct in situ method for labeling the total pool of blood cells in mice by a single intravenous injection of the fluorescent dye CFDA SE (CFSE) is described. The fluorescence intensity of labeled cells initially declines, but remains stable after 4 h, enabling detection weeks after labeling. Labeled leukocytes can be tracked as they accumulate in lymphoid tissues and sites of inflammation and then be immunophenotyped for analysis by flow cytometry. This method is rapid, reproducible and simple to perform.