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Updated: Feb 4, 2026

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
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Published on: September 18, 2013

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Augmentation of Human Monocyte Responses to Lipopolysaccharide by the Protein S and Mer/Tyro3 Receptor Tyrosine

Nicole D Barth1, John A Marwick1, Mary Jo Heeb2

  • 1Medical Research Council Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom; and.

Journal of Immunology (Baltimore, Md. : 1950)
|September 26, 2018
PubMed

Insights

The Tyro3/Axl/Mer (TAM) receptor family and its ligand, protein S, augment monocyte inflammatory responses. This signaling pathway, initiated by protein S binding to monocytes, enhances pro-inflammatory cytokine release, impacting inflammation initiation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Inflammation resolution needs regulated mediator production and inflammatory cell clearance.
  • Mer receptor tyrosine kinase is involved in apoptotic cell phagocytosis (efferocytosis).
  • The Tyro3/Axl/Mer (TAM) receptor family plays roles in immune regulation.

Purpose of the Study:

  • To investigate the expression and function of the TAM receptor family in human monocytes.
  • To understand the interaction of the Mer ligand, protein S, with monocytes.
  • To explore the role of TAM receptor signaling in monocyte inflammatory responses.

Main Methods:

  • Analysis of TAM receptor expression in human monocytes.
  • Assessment of protein S binding to viable monocytes.
  • Investigation of lipopolysaccharide (LPS)-induced cytokine release in monocytes with TAM signaling modulation.

Main Results:

  • Protein S binds to viable monocytes through phosphatidylserine-dependent and -independent mechanisms.
  • Receptor tyrosine kinase signaling augments monocyte cytokine release upon LPS stimulation.
  • TAM-dependent signaling enhances pro-inflammatory cytokine production.

Conclusions:

  • Low-level phosphatidylserine exposure on viable monocytes facilitates protein S binding.
  • Protein S binding to monocytes via TAM receptors augments pro-inflammatory cytokine production.
  • TAM-mediated signaling is crucial in the initiation phase of inflammation.

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