CD47 Binding on Vascular Endothelial Cells Inhibits IL-17-Mediated Leukocyte Adhesion

International Journal of Molecular Sciences

Sharmila Masli¹  Fayaz A. Mir¹  Ian Chin¹  Niharika Singh¹  Ali Hafezi-Moghadam²  Laura Soriano-Romaní³ 

[1] Department of Ophthalmology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA;Molecular Biomarkers Nano-Imaging Laboratory (MBNI), Brigham and Women’s Hospital and Department of Radiology, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA;Ocular Surface Group, IOBA—University of Valladolid, Paseo de Belén 17, 47011 Valladolid, Spain;

关键词: CD47;    chronic ocular inflammation;    leukocyte adhesion;    vascular endothelial cells;    VCAM-1;   

DOI  :  10.3390/ijms23105705

来源: DOAJ

【 摘 要 】

To address the conflicting role of thrombospondin (TSP)-1 reported in acute and chronic pathologies, this study investigated the role of TSP-1 in regulating leukocyte recruitment and regulation of VCAM-1 expression using mouse models of uveitis. The spontaneously increased VCAM-1 expression and leukocyte adhesion in retinas of TSP-1-deficient mice suggested a TSP-1-mediated regulation of VCAM-1 expression. In a chronic uveitis model, induced by immunizing wild-type mice with specific interphotoreceptor retinoid-binding protein (IRBP) peptide, topically applied TSP-1-derived CD47-binding peptide significantly reduced the clinical disease course and retinal leukocyte adhesion as compared to the control peptide-treated group. In contrast, in LPS-mediated acute uveitis, TSP-1 deficiency significantly reduced the retinal leukocyte adhesion. The results of our in vitro study, using vascular endothelial cell (EC) cultures, demonstrate that unlike TNF-α, VCAM-1 expression induced by IL-17 is associated with a reduced expression of endogenous TSP-1. Such reduced endogenous TSP-1 expression in IL-17-stimulated ECs helps limit the CD36-mediated increased VCAM-1 expression, while favoring CD47-mediated inhibition of VCAM-1 expression and leukocyte adhesion. Thus, our study identifies TSP-1:CD47 interaction as a molecular pathway that modulates IL-17-mediated VCAM-1 expression, contributing to its anti-inflammatory effect in chronic inflammatory conditions.

【 授权许可】

Unknown