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Histamine promotes the development of monocyte-derived dendritic cells and reduces tumor growth by targeting the myeloid NADPH oxidase.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 May 15; Vol. 194 (10), pp. 5014-21. Date of Electronic Publication: 2015 Apr 13. - Publication Year :
- 2015
-
Abstract
- The efficiency of immune-mediated clearance of cancer cells is hampered by immunosuppressive mediators in the malignant microenvironment, including NADPH oxidase-derived reactive oxygen species. We aimed at defining the effects of histamine, an inhibitor of the myeloid NADPH oxidase/NOX2, on the development of Ag-presenting dendritic cells (DCs) from myeloid precursors and the impact of these mechanisms for tumor growth. Histamine was found to promote the maturation of human DCs from monocytes by increasing the expression of HLA-DR and costimulatory molecules, which resulted in improved induction of Th cells with Th0 polarity. Experiments using wild-type and NOX2-deficient myelomonoblastic cells showed that histamine facilitated myeloid cell maturation only in cells capable of generating reactive oxygen species. Treatment of mice with histamine reduced the growth of murine EL-4 lymphomas in parallel with an increment of tumor-infiltrating DCs in NOX2-sufficient mice but not in NOX2-deficient (gp91(phox) (-/-)) mice. We propose that strategies to target the myeloid NADPH oxidase may facilitate the development of endogenous DCs in cancer.<br /> (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Cell Differentiation immunology
Coculture Techniques
Dendritic Cells cytology
Flow Cytometry
Humans
Lymphocyte Activation immunology
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Monocytes cytology
Monocytes immunology
Neoplasms, Experimental enzymology
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes immunology
Dendritic Cells immunology
Histamine immunology
NADPH Oxidases immunology
Neoplasms, Experimental immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 194
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 25870245
- Full Text :
- https://doi.org/10.4049/jimmunol.1402991