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Published on: June 23, 2013
Differential expression of platelet-activating factor acetylhydrolase in macrophages and monocyte-derived dendritic
Salma Al-Darmaki1, Harvey A Schenkein, John G Tew
1Clinical Research Center for Periodontal Diseases, Virginia Commonwealth University School of Dentistry, Richmond, VA 23298, USA.
Abstract:
Although macrophages (Mphi) and monocyte-derived dendritic cells (MDDC) come from a common precursor, they are distinct cell types. This report compares the two cell types with respect to the metabolism of platelet-activating factor (PAF), a biologically active lipid mediator. These experiments were prompted by our studies of localized juvenile periodontitis, a disease associated with high IgG2 production and a propensity of monocytes to differentiate into MDDC. As the IgG2 Ab response is dependent on PAF, and MDDC selectively induce IgG2 production, we predicted that PAF levels would be higher in MDDC than in Mphi. To test this hypothesis, human MDDC were prepared by treating adherent monocytes with IL-4 and GM-CSF, and Mphi were produced by culture in M-CSF. Both Mphi and MDDC synthesized PAF; however, MDDC accumulated significantly more of this lipid. We considered the possibility that PAF accumulation in MDDC might result from reduced turnover due to lower levels of PAF acetylhydrolase (PAFAH), the enzyme that catabolizes PAF. Although PAFAH increased when monocytes differentiated into either cell type, MDDC contained significantly less PAFAH than did Mphi and secreted almost no PAFAH activity. The reduced levels of PAFAH in MDDC could be attributed to lower levels of expression of the enzyme in MDDC and allowed these cells to produce PGE(2) in response to exogenous PAF. In contrast, Mphi did not respond in this manner. Together, these data indicate that PAF metabolism may impinge on regulation of the immune response by regulating the accessory activity of MDDC.
Insights
Monocyte-derived dendritic cells (MDDC) accumulate more platelet-activating factor (PAF) than macrophages (Mphi) due to lower PAF acetylhydrolase (PAFAH) levels. This altered lipid metabolism influences immune responses and accessory cell activity.
Area of Science:
- Immunology
- Cell Biology
- Lipid Metabolism
Background:
- Macrophages (Mphi) and monocyte-derived dendritic cells (MDDC) are distinct immune cells originating from a common precursor.
- Platelet-activating factor (PAF) is a critical lipid mediator involved in immune responses, particularly IgG2 antibody production.
- Localized juvenile periodontitis is linked to high IgG2 production and monocyte differentiation into MDDC.
Purpose of the Study:
- To compare the metabolism of platelet-activating factor (PAF) in macrophages (Mphi) and monocyte-derived dendritic cells (MDDC).
- To investigate the role of PAF acetylhydrolase (PAFAH) in regulating PAF levels within these distinct cell types.
- To understand how differences in PAF metabolism might influence immune regulation and accessory cell function.
Main Methods:
- Human MDDC were generated by culturing monocytes with IL-4 and GM-CSF.
- Human Mphi were generated by culturing monocytes with M-CSF.
- PAF synthesis, accumulation, and the activity of PAF acetylhydrolase (PAFAH) were measured in both cell types.
- Prostaglandin E2 (PGE2) production in response to exogenous PAF was assessed.
Main Results:
- Both Mphi and MDDC synthesized PAF, but MDDC accumulated significantly higher levels.
- MDDC exhibited significantly lower levels of PAF acetylhydrolase (PAFAH) activity compared to Mphi.
- Reduced PAFAH expression in MDDC led to increased intracellular PAF and the ability to produce PGE2 in response to exogenous PAF, a response not observed in Mphi.
Conclusions:
- MDDC accumulate higher levels of PAF than Mphi due to decreased catabolism by PAFAH.
- Differential PAF metabolism in MDDC, influenced by PAFAH levels, impacts their accessory cell function.
- PAF metabolism plays a crucial role in regulating immune responses by modulating MDDC activity.
