Neuropeptide S and G protein-coupled receptor 154 modulate macrophage immune responses

Ville Pulkkinen1, Marja-Leena Majuri, Guoying Wang

  • 1Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.

Insights

Neuropeptide S (NPS) and its receptor G protein-coupled receptor 154 (GPR154) are upregulated in asthma. NPS signaling enhances macrophage phagocytosis, suggesting a role for GPR154 in immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Respiratory Medicine

Background:

  • G protein-coupled receptor 154 (GPR154) is a recently identified asthma susceptibility gene.
  • Previous studies showed increased Gpr154 expression in a mouse model of allergic airway inflammation.
  • The expression and function of GPR154 and its ligand neuropeptide S (NPS) in leukocytes remain largely unknown.

Purpose of the Study:

  • To characterize the expression profile of NPS and GPR154 in human leukocytes.
  • To investigate the cellular functions of GPR154 and NPS in immune cells.
  • To determine the role of GPR154 and NPS in a mouse model of allergic airway inflammation.

Main Methods:

  • Real-time RT-PCR was used to analyze NPS and GPR154 mRNA expression in fractionated human blood cells and peripheral blood mononuclear cells (PBMCs).
  • Immunoblotting and immunohistochemistry were employed to confirm GPR154 expression in human leukocytes and sputum.
  • Murine lung tissues and bronchoalveolar lavage (BAL) fluid from ovalbumin (OVA)-challenged mice were analyzed for GPR154 expression.
  • Macrophage cell lines were used to study NPS-stimulated cellular functions.

Main Results:

  • GPR154 was detected in human monocytes/macrophages and eosinophils.
  • Monocyte activation, but not T cell activation, led to increased NPS and GPR154 expression in PBMCs.
  • OVA challenge upregulated GPR154 expression in alveolar macrophages of mice.
  • NPS stimulation induced Gα13- and Gαq-dependent phagocytosis of bacteria in a mouse macrophage cell line.

Conclusions:

  • GPR154 is expressed in specific leukocyte populations, including macrophages and eosinophils.
  • Monocyte activation upregulates NPS and GPR154 expression.
  • GPR154 is upregulated in macrophages during allergic airway inflammation.
  • NPS signaling promotes bacterial phagocytosis by macrophages, indicating a potential role in innate immunity.

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