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Clinical Research Center for Periodontal Diseases, Virginia Commonwealth University School of Dentistry, Richmond, VA 23298
Although macrophages (M
) 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 M
. To test this hypothesis, human MDDC were prepared by treating
adherent monocytes with IL-4 and GM-CSF, and M
were produced by
culture in M-CSF. Both M
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 M
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
PGE2 in response to exogenous PAF. In contrast, M
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.
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