Prior β-blocker treatment decreases leukocyte responsiveness to injury

JCI Insight. 2019 Mar 28;5(9):e99485. doi: 10.1172/jci.insight.99485.

Abstract

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 (β2AR) expression have marked impairments in these processes. β-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 β-blocker treatment on baseline leukocyte parameters and their responsiveness to acute injury. In a temporal and βAR isoform-dependent manner, chronic β-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 β-blocker therapy compared to β-blocker-naïve patients. These results highlight the ability of chronic β-blocker treatment to alter baseline leukocyte characteristics that decrease their responsiveness to acute injury and suggest that prior β-blockade may act to reduce the severity of innate immune responses.

Keywords: Cardiology; Cell migration/adhesion; Cellular immune response; G-protein coupled receptors; Immunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / immunology*
  • Adrenergic beta-Antagonists / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Bone Marrow
  • Cell Adhesion / physiology
  • Cell Movement / physiology
  • Disease Models, Animal
  • Female
  • Humans
  • Immunity, Cellular
  • Leukocytes / immunology*
  • Leukocytes / physiology*
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Protein Isoforms
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism
  • Receptors, CCR2 / metabolism
  • Spleen / metabolism
  • Spleen / pathology
  • Wounds and Injuries / immunology*

Substances

  • Adrenergic beta-Antagonists
  • Ccr2 protein, mouse
  • Protein Isoforms
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-2
  • Receptors, CCR2