Following injury, leukocytes are released from hematopoietic organs and migrate to the site of damage to regulate tissue inflammation and repair; however, leukocytes lacking β2-adrenergic receptor (β2-AR) expression have marked impairments in these processes. Beta 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 beta blocker treatment on baseline leukocyte parameters and their responsiveness to acute injury. In a temporal and β-adrenergic receptor isoform–dependent manner, chronic beta blocker infusion increased splenic vascular cell adhesion molecule 1 expression and leukocyte accumulation (monocytes/macrophages, mast cells, and neutrophils) and decreased chemokine receptor 2 (CCR2) expression and migration of bone marrow and peripheral blood leukocytes (PBLs) to, as well as infiltration into, the heart following acute cardiac injury. Further, CCR2 expression and migratory responsiveness were significantly reduced in the PBLs of patients receiving beta blocker therapy compared with beta blocker–naive patients. These results highlight the ability of chronic beta blocker treatment to alter baseline leukocyte characteristics that decrease leukocytes’ responsiveness to acute injury and suggest that prior beta blockade may act to reduce the severity of innate immune responses.
Laurel A. Grisanti, Claudio de Lucia, Toby P. Thomas, Aron Stark, John T. Strony, Valerie D. Myers, Remus Beretta, Daohai Yu, Celestino Sardu, Raffaele Marfella, Erhe Gao, Steven R. Houser, Walter J. Koch, Eman A. Hamad, Douglas G. Tilley
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