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Platelet-activating factor contributes to immune cell and oxidant-mediated intestinal secretion
T A Hinterleitner1, J D Valentich, J H Cha
1Department of Medicine and Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, USA.
Summary
Platelet-activating factor (PAF) regulates colonic chloride secretion. Hypoxia down-regulates the PAF response, while oxidant and anti-IgE stimuli enhance it, suggesting complex roles in intestinal function.
Area of Science:
- Gastroenterology
- Immunology
- Cellular Physiology
Background:
- Platelet-activating factor (PAF) is a lipid mediator involved in inflammatory and immune responses.
- The role of PAF in regulating colonic ion transport, particularly chloride (Cl-) secretion, is not fully understood.
- Factors like hypoxia and specific immune stimuli may modulate PAF signaling in the colon.
Purpose of the Study:
- To investigate the modulation of PAF-stimulated Cl- secretion in the rat colon.
- To explore the influence of hypoxia on PAF responsiveness.
- To determine the involvement of PAF in Cl- secretion induced by oxidant (H2O2) and anti-immunoglobulin E (anti-IgE) stimuli.
Main Methods:
- Ussing-chamber technique to measure short-circuit current (SCC) in isolated rat and rabbit colons.
- In vitro washing of colonic tissue with albumin-containing Ringer's solution.
- Lipid extraction and addition of extracts to Ussing chambers.
- Administration of exogenous PAF, bradykinin, vasoactive intestinal peptide, and formyl-methionyl-leucyl-phenylalanine (fMLP).
- Use of PAF antagonists and indomethacin.
Main Results:
- Albumin washing enhanced PAF-stimulated Cl- secretion in rat colon.
- Lipid extracts from wash solutions inhibited PAF-stimulated SCC.
- Hypoxia down-regulated the PAF response.
- fMLP-stimulated SCC in rabbit colon was inhibited by indomethacin, not PAF antagonists.
- Anti-IgE and H2O2 stimulated SCC in rat colon, increased PAF production, and were inhibited by PAF antagonists and indomethacin.
Conclusions:
- Hypoxia may release PAF or an endogenous inhibitor, desensitizing colonic PAF receptors.
- PAF is implicated in oxidant and anti-IgE-mediated colonic Cl- secretion.
- PAF does not appear to mediate fMLP-stimulated Cl- secretion via phagocytes in the rabbit colon.