Adhesion of dendritic cells derived from CD34+ progenitors to resting human dermal microvascular endothelial cells is down-regulated upon maturation and partially depends on CD11a-CD18, CD11b-CD18 and CD36.
DC are sentinels of the immune system. In order to reach the skin, bone-marrow-derived DC precursors need to bind and migrate through microvascular endothelial cells. Binding of DC toprimary endothelial cells of the skin has not been investigated. We therefore determined adhesion of DC at different stages of development to human dermal microvascular endothelial cells (HDMEC). DC were derived from CD34+ progenitors in cord blood. To enhance DC maturation, a defined cocktail of IL-1beta+IL-6+TNF-alpha+PGE2 was applied. Adhesion was quantified by fluorimetric and phase-contrast microscopical assays. Significantly more DC precursors (tested on day 5 after isolation) than mature DC (spontaneously matured or cytokine-cocktail-matured and tested on day 13) bound to unstimulated HDMEC. In contrast, the maturation stage of DC had no influence on their binding to human umbilical vein endothelial cells. Pretreatment of HDMEC with TNF-alpha and IFN-gamma resulted in an enhanced attachment of both DC precursors and mature DC. Mature DC lacked expression of CD31, CD36, CD45RA and CLA, and expressed lower levels of CD11a, CD11b and CD49d as compared with precursors tested on day 5. mAb against CD18, CD11a, CD11b, and CD36 markedly inhibited DC binding, whereas anti-CLA, anti-DC-SIGN, anti-CD29 and anti-CD49 mAb did not. Our data support the hypothesis of immunosurveillance with selective recruitment of blood DC precursors to resting and, more so, to inflamed skin. The data have potential relevance for anti-cancer immunotherapy strategies favoring the intracutaneous application of mature DC.
Nguyen
Van Anh
VA
Department of Dermatology and Venereology, University of Innsbruck, Innsbruck, Austria. van.nguyen@uibk.ac.at
Ebner
Susanne
S
Fürhapter
Christina
C
Romani
Nikolaus
N
Kölle
Dieter
D
Fritsch
Peter
P
Sepp
Norbert
N
D018952:Antigens, CD34 / Q000378:metabolism; D040881:CD11a Antigen / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000494:pharmacology; D010641:Phenotype; D011994:Recombinant Proteins; D012867:Skin / Q000098:blood supply / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018952:Antigens, CD34; D040881:CD11a Antigen; D039481:CD11b Antigen; D018821:CD18 Antigens; D018955:CD36 Antigens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma