PMID- 11801647 OWN - NLM STAT- MEDLINE DCOM- 20020212 LR - 20190515 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 168 IP - 3 DP - 2002 Feb 1 TI - Heparin induces differentiation of CD1a+ dendritic cells from monocytes: phenotypic and functional characterization. PG - 1131-8 AB - 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-gamma. The effect of heparin is neutralized by heparin-binding proteins, such as protamine sulfate, platelet factor-4, and beta-thromboglobulin. Functionally, heparin-treated DCs respond to LPS or LPS plus IFN-gamma 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. FAU - Xia, Chang-Qing AU - Xia CQ AD - Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA. FAU - Kao, Kuo-Jang AU - Kao KJ LA - eng GR - HL-58809/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, CD1) RN - 0 (CD1a antigen) RN - 0 (Dextrans) RN - 0 (Growth Substances) RN - 0 (Heparin Antagonists) RN - 0 (Protamines) RN - 0 (fluorescein isothiocyanate dextran) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - 9005-49-6 (Heparin) RN - I223NX31W9 (Fluorescein-5-isothiocyanate) SB - IM MH - Antigens, CD1/*biosynthesis MH - CD4-Positive T-Lymphocytes/drug effects/immunology MH - Cell Culture Techniques/methods MH - Cell Differentiation/drug effects/immunology MH - Cells, Cultured MH - Dendritic Cells/cytology/*drug effects/*immunology/metabolism MH - Dextrans/immunology/metabolism MH - Dose-Response Relationship, Immunologic MH - Fluorescein-5-isothiocyanate/*analogs & derivatives/metabolism MH - Growth Substances/blood/*pharmacology MH - Heparin/blood/*pharmacology MH - Heparin Antagonists/pharmacology MH - Humans MH - Immunophenotyping MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - Lymphocyte Activation/drug effects MH - Monocytes/*cytology/immunology MH - Phagocytosis/drug effects/immunology MH - Protamines/pharmacology EDAT- 2002/01/22 10:00 MHDA- 2002/02/13 10:01 CRDT- 2002/01/22 10:00 PHST- 2002/01/22 10:00 [pubmed] PHST- 2002/02/13 10:01 [medline] PHST- 2002/01/22 10:00 [entrez] AID - 10.4049/jimmunol.168.3.1131 [doi] PST - ppublish SO - J Immunol. 2002 Feb 1;168(3):1131-8. doi: 10.4049/jimmunol.168.3.1131.