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Platelet-activating factor is a general membrane perturbant
1Department of Physiology and Biophysics, Cornell University Medical College, New York, NY 10021.
Abstract:
Platelet-activating factor (PAF) is, at physiological (nanomolar) concentrations, a potent mediator of inflammation and coagulation. At pharmacological (micromolar) concentrations, PAF induces a variety of effects in diverse tissues. Here we show that PAF at micromolar concentrations is a membrane perturbant. Micromolar PAF alters the properties of channels formed by gramicidin A, and at concentrations greater than or equal to 4 microM disrupts the barrier properties of the host lipid bilayer. PAF thus can act as a detergent and non-specifically alter the behavior of membranes and membrane proteins. This may provide an explanation for some of the effects of PAF seen at high concentrations in vitro.
Insights
Platelet-activating factor (PAF) at high concentrations acts like a detergent, disrupting cell membranes and altering protein behavior. This membrane perturbation may explain some of PAF's observed effects in laboratory settings.
Area of Science:
- Biochemistry
- Cell Biology
- Membrane Biophysics
Background:
- Platelet-activating factor (PAF) is a known mediator of inflammation and coagulation at nanomolar concentrations.
- At higher, micromolar concentrations, PAF exhibits diverse effects on various tissues.
Purpose of the Study:
- To investigate the mechanism behind the diverse effects of Platelet-activating factor (PAF) at pharmacological concentrations.
- To determine if PAF acts as a membrane perturbant at micromolar concentrations.
Main Methods:
- Studied the effects of micromolar concentrations of Platelet-activating factor (PAF) on lipid bilayers.
- Investigated alterations in gramicidin A channels in the presence of PAF.
- Assessed the disruption of host lipid bilayer barrier properties by PAF.
Main Results:
- Platelet-activating factor (PAF) at micromolar concentrations functions as a membrane perturbant.
- PAF alters the properties of gramicidin A channels.
- Concentrations of PAF greater than or equal to 4 microM disrupt the barrier properties of lipid bilayers.
Conclusions:
- Platelet-activating factor (PAF) exhibits detergent-like properties at micromolar concentrations.
- PAF non-specifically alters the behavior of membranes and membrane proteins.
- This membrane-perturbing action may explain previously observed in vitro effects of PAF at high concentrations.