title: Endothelial cell-matrix interactions determine maturation of dendritic cells.
abstract: The fate of allo- and xenogeneic endothelial cell (EC) implants is regulated by EC-matrix interactions. While free EC are destroyed by a vigorous immune reaction, EC embedded within 3D collagen cells are well tolerated. Given the critical role DC serve in immune reactivity, we hypothesized that EC-driven DC maturation depends on EC-matrix contact. In marked contrast to DC co-cultured with a cytokine cocktail or with allo- and xenogeneic EC grown to confluence on 2D tissue culture plates, DC exposed to 3D matrix-embedded allo- and xenogeneic EC failed to mature, retaining their endocytic activity and exhibiting significantly reduced expression of maturation markers (costimulatory molecules, HLA-DR, CD83; p <0.01). Matrix-embedded EC also limited cytokine-induced maturation and activity of DC. Incubation with matrix-embedded EC inhibited DC induction of allogeneic lymphocyte proliferation (p <0.002) and EC cross-activation (ICAM-1, VCAM-1, HLA-DR, TLR2 and 4; p <0.01). The endothelium in its quiescent state is confluent and substrate adherent. The former ensures secretion of growth inhibitors rather than promoters, and the latter may ensure immune acceptance. We now demonstrate for the first time that interactions of EC with an underlying 3D matrix affect the ability of EC to drive DC maturation.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. hmethe@mit.edu
authors.forename: Heiko
authors.initials: H
authors.lastname: Methe
authors.forename: Shmuel
authors.initials: S
authors.lastname: Hess
authors.forename: Elazer R
authors.initials: ER
authors.lastname: Edelman
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D020239:Receptor Cross-Talk / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D003094:Collagen