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Extra- and intracellular metabolism of platelet-activating factor by cultured mesangial cells

R Neuwirth1, N Ardaillou, D Schlondorff

  • 1Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.

The American Journal of Physiology
|April 1, 1989
PubMed

Insights

Human and rat mesangial cells generate and metabolize platelet-activating factor (PAF). An ectoenzymatic acetylhydrolase on the cell surface rapidly inactivates PAF, protecting cells from its effects.

Area of Science:

  • Nephrology
  • Cell Biology
  • Biochemistry

Background:

  • Platelet-activating factor (PAF) plays a role in glomerular inflammation.
  • Understanding PAF metabolism in mesangial cells is crucial for kidney research.

Purpose of the Study:

  • To investigate the metabolism of PAF in cultured human and rat mesangial cells.
  • To identify the location and characteristics of PAF-metabolizing enzymes.

Main Methods:

  • Cultured human and rat mesangial cells were used.
  • Cells were stimulated with A23187 to induce PAF generation.
  • [3H]-labeled PAF was used to trace metabolism.
  • Extracellular and intracellular metabolism were analyzed separately.
  • Enzyme activity was assessed using trypsinization and substrate specificity tests.

Main Results:

  • Both human and rat mesangial cells generated PAF.
  • Cells rapidly hydrolyzed extracellular and intracellular PAF to lyso-PAF.
  • A significant portion of PAF metabolism occurred extracellularly.
  • Acetylhydrolase activity was predominantly located on the outer cell surface (ectoenzyme).
  • This ectoenzyme activity was distinct from phospholipase A2.

Conclusions:

  • Rat and human mesangial cells possess the capacity to both generate and metabolize PAF.
  • An ectoenzymatic acetylhydrolase on mesangial cell surfaces is key for rapid PAF inactivation.
  • This ectoenzyme likely protects glomerular cells from the harmful effects of PAF.

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