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The antibiotic polymyxin B modulates P2X7 receptor function

Davide Ferrari1, Cinzia Pizzirani, Elena Adinolfi

  • 1Department of Experimental and Diagnostic Medicine, Sections of General Pathology, University of Ferrara, Italy. dfr@unife.it

Journal of Immunology (Baltimore, Md. : 1950)
|September 24, 2004
PubMed

Insights

Polymyxin B (PMB) enhances P2X7 receptor responses to nucleotides, increasing cell permeability and death. This suggests PMB can potentiate P2X7-mediated effects, impacting immune cell studies and potential therapies.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Polymyxin B (PMB) is an antibiotic known for neutralizing bacterial lipopolysaccharide (LPS).
  • The P2X7 receptor (P2X7R) is involved in various cellular processes and immune responses.

Purpose of the Study:

  • To investigate the effect of Polymyxin B on P2X7 receptor-mediated responses.
  • To explore the potential of PMB in modulating P2X7R activity in different cell types, including cancer cells.

Main Methods:

  • Experiments were conducted on HEK293 and K562 cells transfected with P2X7 cDNA, as well as mouse and human macrophages.
  • The study examined B lymphocytes from chronic lymphocytic leukemia patients.
  • Cellular responses to nucleotide stimulation in the presence and absence of PMB were measured, including calcium influx, membrane permeabilization, and cytotoxicity.

Main Results:

  • Polymyxin B significantly potentiated nucleotide-mediated P2X7R stimulation across various cell types.
  • ATP-induced calcium influx, plasma membrane permeabilization, and cytotoxicity were markedly enhanced by PMB.
  • The synergistic effect was blocked by oxidized ATP (oATP) but not KN-62, confirming P2X7R involvement.
  • Cells lacking P2X7R were insensitive to the combined PMB and ATP treatment.
  • PMB did not adversely affect cell viability at the tested concentrations.

Conclusions:

  • Polymyxin B acts as a potent modulator of P2X7 receptor function.
  • The findings suggest caution when interpreting ATP-stimulated immune cell responses in the presence of PMB due to potential LPS contamination or direct P2X7R potentiation.
  • PMB could be a valuable tool for research involving P2X7R modulation and potentially in therapeutic strategies targeting P2X7R-expressing cells.

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