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P2 purinoceptors in the immune system
F Di Virgilio1, D Ferrari, S Falzoni
1Institute of General Pathology, University of Ferrara, Italy.
Ciba Foundation Symposium
|January 1, 1996
Summary
Immune cells utilize ionotropic receptors for extracellular nucleotides, recognizing ATP4- as a preferred ligand. These receptors exhibit varied permeability and can trigger cytokine release or cell death upon activation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Pharmacology
Background:
- Immune cells express plasma membrane receptors for extracellular nucleotides.
- Both G protein-linked metabotropic and channel-forming ionotropic receptors are known, but no P2 receptor subtype has been cloned from immune cells.
- Metabotropic receptors are found in human B cells but not T cells, and not in mouse B and T cells.
Purpose of the Study:
- To characterize the ionotropic receptors in various immune cells.
- To investigate the functional properties, pharmacology, and permeability of these receptors.
- To explore the modulation of these receptors by cytokines and differentiation, and their role in immune cell responses.
Main Methods:
- Pharmacological characterization of ionotropic receptors in human and mouse lymphocytes, macrophages, microglial cells, and rat mast cells.
- Assessment of receptor permeability using charged molecules of varying molecular mass.
- Investigation of receptor modulation by inflammatory cytokines (IL-2, gamma-interferon) and during monocyte to macrophage differentiation.
- Analysis of cellular responses, including IL-1 beta release and cell death (necrosis/apoptosis), following receptor stimulation.
Main Results:
- Ionotropic receptors recognizing ATP4- as the preferred ligand are ubiquitously expressed in immune cells.
- Pharmacological profiles are similar across immune cells, but permeability differs: lymphocytes have a 200-300 Da cut-off, while macrophages, microglial cells, and mast cells have a 900 Da cut-off.
- Receptors are modulated by cytokines and differentiation; transient stimulation induces IL-1 beta release in macrophages/microglial cells, and sustained activation causes cell death.
Conclusions:
- Immune cells express functionally distinct ionotropic nucleotide receptors.
- These receptors play a role in immune cell signaling, cytokine release, and cell fate determination.
- Understanding these receptors offers potential therapeutic targets in immune-related diseases.