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Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610
Dendritic cells (DCs) play important roles in initiation and
regulation of immune responses. DCs derived from human monocytes can be
classified according to presence of CD1a molecules. Although
CD1a+ DCs can be prepared from monocytes in media
containing GM-CSF, IL-4, and FCS, it has been reported that
CD1a+ DCs could not be easily obtained from monocytes using
media containing human serum or plasma. In this study, we demonstrate
for the first time that heparin can reliably induce differentiation of
CD1a+ DCs from monocytes with or without autologous serum
or plasma. The development of CD1a+ DCs is heparin
concentration dependent (0–50 U/ml). Comparing with CD1a-
DCs developed without heparin, CD1a+ DCs express higher
CD40 and CD80 and lower CD86. Both CD1a+ and
CD1a- DCs express similar levels of HLA-DR. CD80, CD86,
HLA-DR, and CD40 are proportionally up-regulated when both types of DCs
are stimulated with LPS or LPS plus IFN-
. The effect of heparin is
neutralized by heparin-binding proteins, such as protamine sulfate,
platelet factor-4, and 
-thromboglobulin. Functionally,
heparin-treated DCs respond to LPS or LPS plus IFN- with higher
IL-10 and less IL-12 production than heparin-untreated DCs.
Heparin-treated DCs are more potent in priming allogeneic and
autologous CD4+ T cells to proliferate and to produce both
type 1 and type 2 cytokines. The results of our study show that
CD1a+ DCs can be prepared from monocytes ex vivo without
using xenogeneic serum and may be used for
immunotherapy.
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