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Harvesting Murine Alveolar Macrophages and Evaluating Cellular Activation Induced by Polyanhydride Nanoparticles
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Protein tyrosine kinase but not protein kinase C inhibition blocks receptor induced alveolar macrophage activation

K Pollock1, M T Withnall

  • 1Rhône-Poulenc Rorer Ltd Dagenham Research Centre Rainham Road South Essex Dagenham RM10 7XS UK.

Mediators of Inflammation
|January 1, 1993
PubMed

Insights

Protein tyrosine kinase (PTK) activation is crucial for inflammatory mediator release in guinea-pig macrophages stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP). Protein kinase C (PKC) is involved in lipopolysaccharide (LPS) priming but not FMLP signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • N-formyl-methionyl-leucyl-phenylalanine (FMLP) is a key chemoattractant that triggers inflammatory responses in macrophages.
  • Superoxide anion and thromboxane B(2) (TXB(2)) are critical inflammatory mediators released by macrophages.
  • Protein tyrosine kinase (PTK) and protein kinase C (PKC) are signaling enzymes implicated in cellular activation.

Purpose of the Study:

  • To investigate the roles of PTK and PKC in FMLP-induced superoxide and TXB(2) generation in guinea-pig alveolar macrophages (AM).
  • To elucidate the signaling pathways involved in macrophage activation by FMLP and lipopolysaccharide (LPS).

Main Methods:

  • Utilized selective enzyme inhibitors genistein (for PTK) and Ro 31-8220 (for PKC).
  • Measured superoxide anion and TXB(2) release in guinea-pig AM stimulated with FMLP and/or phorbol myristate acetate (PMA) and LPS.
  • Assessed dose-dependent inhibition and potentiation effects of the inhibitors.

Main Results:

  • Genistein significantly inhibited FMLP-induced superoxide and TXB(2) generation, indicating PTK's essential role.
  • Ro 31-8220 inhibited PMA-induced superoxide but had minimal or potentiating effects on FMLP responses.
  • Ro 31-8220 inhibited TXB(2) release when present during LPS priming and FMLP challenge, suggesting PKC's role in priming.

Conclusions:

  • PTK activation is indispensable for FMLP-mediated generation of superoxide and TXB(2) in AM.
  • PKC activation is necessary for LPS priming but appears to negatively modulate FMLP signal transduction.
  • These findings clarify the distinct roles of PTK and PKC in macrophage inflammatory responses.

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