Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis
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Abstract
- Endothelial cells play significant roles in conditioning tissues after injury by the production and secretion of angiocrine factors. At least two distinct subsets of monocytes, CD45(+)CD11b(+)Gr1(+)Ly6C(+) inflammatory and CD45(+)CD11b(+)Gr1(-)Ly6C(-) anti-inflammatory monocytes, respond differentially to these angiocrine factors and promote pathogen/debris clearance and arteriogenesis/tissue regeneration, respectively. We demonstrate here that local sphingosine 1-phosphate receptor 3 (S1P(3)) agonism recruits anti-inflammatory monocytes to remodeling vessels. Poly(lactic-co-glycolic acid) thin films were used to deliver FTY720, an S1P(1/3) agonist, to inflamed and ischemic tissues, which resulted in a reduction in proinflammatory cytokine secretion and an increase in regenerative cytokine secretion. The altered balance of cytokine secretion results in preferential recruitment of anti-inflammatory monocytes from circulation. The chemotaxis of these cells, which expressmore S1P(3) than inflammatory monocytes, toward SDF-1 alpha was also enhanced with FTY720 treatment, but not in S1P(3) knockout cells. FTY720 delivery enhanced arteriolar diameter expansion and increased length density of the local vasculature. This work establishes a role for S1P receptor signaling in the local conditioning of tissues by angiocrine factors that preferentially recruit regenerative monocytes that can enhance healing outcomes, tissue regeneration, and biomaterial implant functionality.
| Title | Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis |
|---|---|
| Creator | Sefcik Anderson, Lauren |
| Ogle, M. E. | |
| Peirce-Cottler, S. M. | |
| Martin, K. | |
| Bowers, D. T. | |
| Lynch, K. R. | |
| Awojoodu, A. O. | |
| Brayman, K. L. | |
| Botchwey, E. | |
| Publisher | Proceedings of the National Academy of Sciences |
| Academic Department | Chemical & Biomolecular Engineering |
| Division | Engineering |
| Organization | Lafayette College |
| Date Issued | 2013 |
| Date Available | 2018-12-20T21:03:17Z |
| Type | Article |
| Language | English |
| Keyword | microvascular remodeling |
| immunomodulation | |
| sphingolipid | |
| biomaterials | |
| tissue engineering | |
| Bibliographic Citation | Awojoodu, A. O. (2013) " Sphingosine 1-phosphate receptor 3 regulates recruitment of anti-inflammatory monocytes to microvessels during implant arteriogenesis." Proceedings of the National Academy of Sciences 110 (34): 13785-13790. |
| Standard Identifier | DOI 10.1073/pnas.1221309110 |
| Handle 10385/2486 | |
| Permalink | http://hdl.handle.net/10385/2486 |
| Rights Statement |
Creative Commons - Attribution, Non-Commercial, No Derivatives
|
| Rights Holders | Sefcik Anderson, Lauren |
| Ogle, M. E. | |
| Peirce-Cottler, S. M. | |
| Botchwey, E. | |
| Bowers, D. T. | |
| Lynch, K. R. | |
| Awojoodu, A. O. | |
| Brayman, K. L. | |
| Martin, K. |
Contains
| File | SefcikAnderson-ProceedingsoftheNationalAcademyofSciences-vol110-2013.pdf | Uploaded 2019-10-20 | Public | Download |
| File | SefcikAnderson-ProceedingsoftheNationalAcademyofSciences-vol110-2013-supp.pdf | Uploaded 2020-01-03 | Public | Download |
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