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Activated mast cells release extracellular type platelet-activating factor acetylhydrolase that contributes to
K Nakajima1, M Murakami, R Yanoshita
1Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Japan.
Abstract:
IgE-dependent and -independent activation of mouse bone marrow-derived mast cells (BMMC) elicited rapid and transient production of platelet-activating factor (PAF), which reached a maximal level by 2-5 min and was then degraded rapidly, returning to base-line levels by 10-20 min. Inactivation of PAF was preceded by the release of PAF acetylhydrolase (PAF-AH) activity, which reached a plateau by 3-5 min and paralleled the release of beta-hexosaminidase, a marker of mast cell exocytosis. Immunochemical and molecular biological studies revealed that the PAF-AH released from activated mast cells was identical to the plasma-type isoform. In support of the autocrine action of exocytosed PAF-AH, adding exogenous recombinant plasma-type PAF-AH markedly reduced PAF accumulation in activated BMMC. Furthermore, culture of BMMC with a combination of c-kit ligand, interleukin-1beta and interleukin-10 for > 24 h led to an increase in plasma-type PAF-AH expression, accompanied by a reduction in stimulus-initiated PAF production. Collectively, these results suggest that plasma-type PAF-AH released from activated mast cells sequesters proinflammatory PAF produced by these cells, thereby revealing an intriguing anti-inflammatory aspect of mast cells.
Insights
Mast cells rapidly produce and degrade platelet-activating factor (PAF). Released PAF acetylhydrolase (PAF-AH) inactivates PAF, suggesting mast cells have an anti-inflammatory role in controlling PAF.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Mast cells play a key role in inflammatory responses.
- Platelet-activating factor (PAF) is a potent lipid mediator involved in inflammation.
- The regulation of PAF levels by mast cells is not fully understood.
Purpose of the Study:
- To investigate the production and release of PAF by mast cells.
- To identify the enzyme responsible for PAF inactivation.
- To explore the potential anti-inflammatory role of mast cell-derived factors.
Main Methods:
- Activation of mouse bone marrow-derived mast cells (BMMC) using IgE-dependent and -independent stimuli.
- Measurement of PAF production and degradation.
- Assay of PAF acetylhydrolase (PAF-AH) activity.
- Immunochemical and molecular biological characterization of released PAF-AH.
- Treatment of BMMC with recombinant PAF-AH.
- Long-term culture of BMMC with cytokines (c-kit ligand, IL-1β, IL-10) to assess PAF-AH expression.
Main Results:
- Activated BMMC rapidly produced and degraded PAF.
- PAF inactivation was mediated by released PAF-AH, identified as the plasma-type isoform.
- Exogenous PAF-AH reduced PAF accumulation in activated BMMC.
- Cytokine-induced culture of BMMC increased plasma-type PAF-AH expression and reduced PAF production.
Conclusions:
- Mast cells release plasma-type PAF-AH, which inactivates pro-inflammatory PAF.
- This mechanism suggests an autocrine anti-inflammatory function for mast cells.
- Mast cell-derived PAF-AH plays a critical role in regulating local PAF levels and mitigating inflammation.