ß-adrenergic stimulation increases macrophage CD14 expression and E. coli phagocytosis through PKA signaling

Kuzhali Muthu1, Li-K He, Andrea Szilagyi

  • 1Department of Surgery, Loyola University Medical Center, Maywood, IL 60153, USA. kmuthu@lumc.edu

Insights

Beta-adrenergic stimulation, like with isoproterenol, boosts CD14 expression and bacterial phagocytosis in mouse bone marrow macrophages (BMØ). This pathway involves cAMP-dependent PKA, highlighting potential therapeutic roles for beta-adrenergic agents in innate immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • CD14 glycoprotein binds bacterial lipopolysaccharide (LPS) in macrophages (MØ), crucial for innate immunity.
  • Elevated catecholamine (CA) levels during critical injury and sepsis impact MØ inflammatory functions.
  • The role of beta-adrenergic stimulation on CD14 expression and phagocytosis in MØ remains unclear.

Purpose of the Study:

  • To investigate the hypothesis that beta-adrenergic stimulation regulates CD14 expression and bacterial phagocytosis in mouse bone marrow macrophages (BMØ).

Main Methods:

  • Murine BMØ were stimulated with isoproterenol.
  • Inhibitor studies using H-89 (PKA inhibitor) and gene-silencing (siRNA) were performed.
  • Bacterial phagocytosis was assessed using live Escherichia coli uptake.
  • Experiments utilized CD14-deficient (CD14(-/-)) mice.

Main Results:

  • Isoproterenol induced a dose-dependent increase in cell surface CD14 expression in BMØ.
  • The response was mediated by cAMP-dependent protein kinase A (PKA).
  • Increased CD14 expression correlated with enhanced E. coli uptake, dependent on CD14.
  • Isoproterenol-mediated phagocytosis and CD14 expression shared similar EC50 values.

Conclusions:

  • Beta-adrenergic stimulation significantly increases CD14 expression and bacterial phagocytosis in BMØ.
  • This effect is mediated by a common signaling pathway involving cAMP-dependent PKA.
  • Beta-adrenergic agents may represent a potential therapeutic strategy to modulate innate immune functions.

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