PMID- 15833768 OWN - NLM STAT- MEDLINE DCOM- 20060223 LR - 20240312 IS - 1530-6860 (Electronic) IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 19 IP - 9 DP - 2005 Jul TI - Thrombospondin-1 up-regulates expression of cell adhesion molecules and promotes monocyte binding to endothelium. PG - 1158-60 AB - Expression of cell adhesion molecules (CAM) responsible for leukocyte-endothelium interactions plays a crucial role in inflammation and atherogenesis. Up-regulation of vascular CAM-1 (VCAM-1), intracellular CAM-1 (ICAM-1), and E-selectin expression promotes monocyte recruitment to sites of injury and is considered to be a critical step in atherosclerotic plaque development. Factors that trigger this initial response are not well understood. As platelet activation not only promotes thrombosis but also early stages of atherogenesis, we considered the role of thrombospondin-1 (TSP-1), a matricellular protein released in abundance from activated platelets and accumulated in sites of vascular injury, as a regulator of CAM expression. TSP-1 induced expression of VCAM-1 and ICAM-1 on endothelium of various origins, which in turn, resulted in a significant increase of monocyte attachment. This effect could be mimicked by a peptide derived from the C-terminal domain of TSP-1 and known to interact with CD47 on the cell surface. The essential role of CD47 in the cellular responses to TSP-1 was demonstrated further using inhibitory antibodies and knockdown of CD47 with small interfering RNA. Furthermore, we demonstrated that secretion of endogenous TSP-1 and its interaction with CD47 on the cell surface mediates endothelial response to the major proinflammatory agent, tumor necrosis factor alpha (TNF-alpha). Taken together, this study identifies a novel mechanism regulating CAM expression and subsequent monocyte binding to endothelium, which might influence the development of anti-atherosclerosis therapeutic strategies. FAU - Narizhneva, Natalya V AU - Narizhneva NV AD - Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. FAU - Razorenova, Olga V AU - Razorenova OV FAU - Podrez, Eugene A AU - Podrez EA FAU - Chen, Juhua AU - Chen J FAU - Chandrasekharan, Unni M AU - Chandrasekharan UM FAU - DiCorleto, Paul E AU - DiCorleto PE FAU - Plow, Edward F AU - Plow EF FAU - Topol, Eric J AU - Topol EJ FAU - Byzova, Tatiana V AU - Byzova TV LA - eng GR - R01 HL071625/HL/NHLBI NIH HHS/United States GR - RR-00080/RR/NCRR NIH HHS/United States GR - HL071625./HL/NHLBI NIH HHS/United States GR - M01 RR000080/RR/NCRR NIH HHS/United States GR - P50 HL077107/HL/NHLBI NIH HHS/United States GR - P50 HL77107/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050415 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (CD47 Antigen) RN - 0 (CD47 protein, human) RN - 0 (Cell Adhesion Molecules) RN - 0 (E-Selectin) RN - 0 (NF-kappa B) RN - 0 (RNA, Small Interfering) RN - 0 (Recombinant Proteins) RN - 0 (Thrombospondin 1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Atherosclerosis/etiology MH - CD47 Antigen/physiology MH - Cell Adhesion MH - Cell Adhesion Molecules/*genetics MH - Cells, Cultured MH - E-Selectin/genetics MH - Endothelial Cells/cytology/*metabolism MH - *Gene Expression Regulation/drug effects MH - Humans MH - Intercellular Adhesion Molecule-1/genetics MH - Monocytes/*physiology MH - NF-kappa B/metabolism MH - RNA, Small Interfering/pharmacology MH - Recombinant Proteins/pharmacology MH - Thrombospondin 1/*physiology MH - Tumor Necrosis Factor-alpha/pharmacology MH - Up-Regulation MH - Vascular Cell Adhesion Molecule-1/genetics PMC - PMC1569946 MID - NIHMS9154 EDAT- 2005/04/19 09:00 MHDA- 2006/02/24 09:00 PMCR- 2008/01/28 CRDT- 2005/04/19 09:00 PHST- 2005/04/19 09:00 [pubmed] PHST- 2006/02/24 09:00 [medline] PHST- 2005/04/19 09:00 [entrez] PHST- 2008/01/28 00:00 [pmc-release] AID - 04-3310fje [pii] AID - 10.1096/fj.04-3310fje [doi] PST - ppublish SO - FASEB J. 2005 Jul;19(9):1158-60. doi: 10.1096/fj.04-3310fje. Epub 2005 Apr 15.