Generation of phagocytic MAK and MAC-DC for therapeutic use: Characterization and in vitro functional properties

Phagocytic cells with macrophage or dendritic cell phenotype, able to capture and ingest tumor cells, were derived in large numbers from peripheral blood mononuclear cells using two different activation procedures. Peripheral blood mononuclear cells were stimulated in nonadherent conditions in the p...

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Published in:	Experimental hematology 1999-04, Vol.27 (4), p.751-761
Main Authors:	Boyer, Aurélie, Andreu, Georges, Romet-Lemonne, Jean-Loup, Fridman, Wolf-Herman, Teillaud, Jean-Luc
Format:	Article
Language:	eng
Subjects:	Antibody-Dependent Cell Cytotoxicity Antigens, CD - biosynthesis Calcitriol - pharmacology Cell cytotoxicity—Dendritic cells—Macrophages—Phagocytosis—FcγR Cell Differentiation - drug effects Cell Differentiation - immunology Cells, Cultured Cytotoxicity Tests, Immunologic Dendritic Cells - cytology Dendritic Cells - drug effects Dendritic Cells - immunology Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology Humans Immunophenotyping Interleukin-13 - pharmacology Leukocytes, Mononuclear - cytology Leukocytes, Mononuclear - drug effects Lymphocyte Activation - drug effects Lymphocyte Activation - immunology Macrophages - cytology Macrophages - drug effects Macrophages - immunology Phagocytosis - drug effects Saccharomyces cerevisiae
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Summary:	Phagocytic cells with macrophage or dendritic cell phenotype, able to capture and ingest tumor cells, were derived in large numbers from peripheral blood mononuclear cells using two different activation procedures. Peripheral blood mononuclear cells were stimulated in nonadherent conditions in the presence of human AB serum with either granulocyte-macrophage colony-stimulating factor and dihydroxy-vitamin D 3 for 7 days and with interferon-gamma for the last 18 hours to obtain activated macrophages (MAK) or with granulocyte-macrophage colony-stimulating factor and interleukin-13 for 7 days (with fresh interleukin-13 added on day 4) to obtain macrophage-dendritic cells (MAC-DC). A strong ability of MAC-DC to phagocytose yeasts was observed, in contrast to a low–intermediate phagocytosis capacity by MAK. Both CD14 + FCγR + (FcγRI/CD64, FcγRII/CD32, FcγRIII/CD16) MAK and CD1a + /CD86 + , CD14 − MAC-DC were able to phagocytose whole tumor cells. However, only MAK phagocytosis was enhanced by FcγR engagement. MAK but not MAC-DC could lyse tumor cell in antibody-dependent cell cytotoxicity assays, via FcγRI. Thus, MAK as well as MAC-DC may represent valuable tools for different in vivo therapy strategies that do or do not include the use of monoclonal antibodies.
ISSN:	0301-472X 1873-2399