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JCI Insight ; 52019 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-30920389

RESUMEN

Following injury, leukocytes are released from hematopoietic organs and migrate to the site of damage to regulate tissue inflammation and repair, however leukocytes lacking ß2-adrenergic receptor (ß2AR) expression have marked impairments in these processes. ß-blockade is a common strategy for the treatment of many cardiovascular etiologies, therefore the objective of our study was to assess the impact of prior ß-blocker treatment on baseline leukocyte parameters and their responsiveness to acute injury. In a temporal and ßAR isoform-dependent manner, chronic ß-blocker infusion increased splenic vascular cell adhesion molecule-1 (VCAM-1) expression and leukocyte accumulation (monocytes/macrophages, mast cells and neutrophils) and decreased chemokine receptor 2 (CCR2) expression, migration of bone marrow cells (BMC) and peripheral blood leukocytes (PBL), as well as infiltration into the heart following acute cardiac injury. Further, CCR2 expression and migratory responsiveness was significantly reduced in the PBL of patients receiving ß-blocker therapy compared to ß-blocker-naïve patients. These results highlight the ability of chronic ß-blocker treatment to alter baseline leukocyte characteristics that decrease their responsiveness to acute injury and suggest that prior ß-blockade may act to reduce the severity of innate immune responses.


Asunto(s)
Antagonistas Adrenérgicos beta/inmunología , Antagonistas Adrenérgicos beta/metabolismo , Leucocitos/inmunología , Leucocitos/fisiología , Heridas y Lesiones/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Médula Ósea , Adhesión Celular/fisiología , Movimiento Celular/fisiología , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunidad Celular , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Isoformas de Proteínas , Receptores Adrenérgicos beta/metabolismo , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Receptores CCR2/metabolismo , Bazo/metabolismo , Bazo/patología
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