title: Thrombospondin-1-N-terminal domain induces a phagocytic state and thrombospondin-1-C-terminal domain induces a tolerizing phenotype in dendritic cells.
abstract: In our previous study, we have found that thrombospondin-1 (TSP-1) is synthesized de novo upon monocyte and neutrophil apoptosis, leading to a phagocytic and tolerizing phenotype of dendritic cells (DC), even prior to DC-apoptotic cell interaction. Interestingly, we were able to show that heparin binding domain (HBD), the N-terminal portion of TSP-1, was cleaved and secreted simultaneously in a caspase- and serine protease- dependent manner. In the current study we were interested to examine the role of HBD in the clearance of apoptotic cells, and whether the phagocytic and tolerizing state of DCs is mediated by the HBD itself, or whether the entire TSP-1 is needed. Therefore, we have cloned the human HBD, and compared its interactions with DC to those with TSP-1. Here we show that rHBD by itself is not directly responsible for immune paralysis and tolerizing phenotype of DCs, at least in the monomeric form, but has a significant role in rendering DCs phagocytic. Binding of TSP-1-C-terminal domain on the other hand induces a tolerizing phenotype in dendritic cells.
authors.affiliation: The Laboratory for Cellular and Molecular Immunology, Rheumatology Research Unit, and The Protein Expression and Protein Purification Facilities, Hebrew University and Hadassah University Medical Center, Jerusalem, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Tabib
authors.forename: Alon
authors.initials: A
authors.lastname: Krispin
authors.forename: Uriel
authors.initials: U
authors.lastname: Trahtemberg
authors.forename: Inna
authors.initials: I
authors.lastname: Verbovetski
authors.forename: Mario
authors.initials: M
authors.lastname: Lebendiker
authors.forename: Tsafi
authors.initials: T
authors.lastname: Danieli
authors.forename: Dror
authors.initials: D
authors.lastname: Mevorach
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D003713:Dendritic Cells / Q000166:cytology*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D010587:Phagocytosis / Q000502:physiology*; D010641:Phenotype; D019700:Thrombospondin 1 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
chemical_list: D017931:DNA Primers; D019700:Thrombospondin 1; D006493:Heparin