Abstract 110: The Role Of Sphingosine-1-Phosphate In The Reverse Transendothelial Migration Of Aortic Intimal Myeloid Cells
العنوان: | Abstract 110: The Role Of Sphingosine-1-Phosphate In The Reverse Transendothelial Migration Of Aortic Intimal Myeloid Cells |
---|---|
المؤلفون: | Chanele K Polenz, Corey A Scipione, Sharon Hyduk, Myron I Cybulsky |
المصدر: | Arteriosclerosis, Thrombosis, and Vascular Biology. 42 |
بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2022. |
سنة النشر: | 2022 |
مصطلحات موضوعية: | Cardiology and Cardiovascular Medicine |
الوصف: | CD11c + myeloid cells (MCs) reside in the normal aortic arch intima at regions predisposed to atherosclerosis. We showed that reverse transendothelial migration (RTM) of these intimal MCs into the arterial circulation is a protective immune response. RTM is triggered by systemic stimulation of cytokine and toll-like receptors (TLRs), e.g., TLR4 by lipopolysaccharide (LPS), and is inhibited by hypercholesterolemia and associated intimal MC lipid accumulation. We hypothesize that signaling by sphingosine-1-phosphate (S1P) and its receptors (S1PRs) is required for RTM of intimal MCs following systemic stimulation of TLRs, analogous to its role in immune cell trafficking in lymphoid tissues. In the lesser curvature of the aortic arch of wild type C57BL/6 mice, LPS induced the expression of S1P receptors 1 & 3, and sphingosine kinase 1 (SphK1). FTY720, a broad-spectrum S1P receptor modulator, blocked LPS-induced RTM, as determined by the enumeration of CD11c+ MCs by en face immunoconfocal microscopy. S1PR1 or S1PR3 inhibitors blocked RTM in a partial and additive manner, suggesting a role for both S1P receptors in intimal MC migration. Initial experiments show that Cre-mediated deletion of S1PR1 in myeloid cells partially blocks LPS-induced RTM, suggesting that myeloid-specific S1PR1 signaling is implicated in the migratory process. Furthermore, global loss or hematopoietic deficiency of SPHK1 reduced the abundance of CD11c+ MCs in the aortic intima, suggesting an additional role for myeloid S1P production in the homeostatic maintenance of resident aortic immune cells. Cre-mediated deletion of S1PR1 in endothelial cells also reduced the abundance of intimal MCs, providing further evidence that S1P signaling in the intima is important in maintaining the intimal MC population. Thus, functional and expression studies suggest that S1P signaling plays a role in both the maintenance of resident intimal MCs and LPS-induced RTM. |
تدمد: | 1524-4636 1079-5642 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::dc412eba627ef26a6522e04a5967ec23 https://doi.org/10.1161/atvb.42.suppl_1.110 |
رقم الأكسشن: | edsair.doi...........dc412eba627ef26a6522e04a5967ec23 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15244636 10795642 |
---|