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Immune System Imaging
Published in Margarida M. Barroso, Xavier Intes, In Vivo, 2020
Michael J. Hickey, M. Ursula Norman
After undergoing antigen-mediated activation within lymph nodes, T cells leave the lymph nodes via the lymphatic vasculature, eventually entering the bloodstream to undergo recirculation. Imaging has also revealed the mechanisms underlying lymphocyte egress from the lymph node, demonstrating that T cells migrate toward and within the lymph node sinus at which stage they are able to be captured by lymph flow (Grigorova et al., 2009). This process is driven by interaction of sphingosine 1-phosphate (S1P), a chemoattractant abundant in lymph, via interaction with T cell-expressed sphingosine 1-phosphate receptor type 1 (S1P1). The latter finding is notable for the fact that prevention of T cell egress from the lymph node via S1P1 inhibition forms the basis of action of Fingolimod (FTY720), an immunosuppressive agent used in the treatment of multiple sclerosis (Calabresi et al., 2014).
Stem Cell Engineering Using Bioactive Molecules for Bone-Regenerative Medicine
Published in Gilson Khang, Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine, 2017
S1P is a 379.47 Da endogenous sphingolipid signaling molecule composed of a phosphate head group attached to sphingosine, an amino alcohol containing an unsaturated 18-carbon chain. S1P signaling covers a wide range of cellular processes, including migration,77 cell motility,78 proliferation,77 and survival.79 Moreover, S1P is implicated in many processes relating to bone homeostasis and wound healing, such as angiogenesis,80 vascular maturation,81 inflammation,82 immune cell trafficking and differentiation,83 and stem cell trafficking.84 The therapeutic application of S1P signaling small molecules can be applied to enhancing bone allograft incorporation, in which graft vascularization plays a critical role in graft success.85 In a rat cranial defect model, FTY720 and poly(lacticco-glycolic acid) (PLGA)-coated allografts significantly enhanced new bone formation compared to controls. FTY720 allografts promoted bridging between host and donor bone to promote osseous integration of the allograft.86 Others have investigated the role of S1P signaling in critical bone-remodeling processes such as osteoblastogenesis and osteoclastogenesis. Both S1P and FTY720 enhance the BMP-2-induced osteogenic differentiation of C2C12 myoblasts through increased phosphorylation of ERK1/2 and Smad1/5/8, key downstream regulators of osteogenesis.87
Longitudinal metabolic alterations in plasma of rats exposed to low doses of high linear energy transfer radiation
Published in Journal of Environmental Science and Health, Part C, 2021
Tixieanna Dissmore, Andrew G DeMarco, Meth Jayatilake, Michael Girgis, Shivani Bansal, Yaoxiang Li, Khyati Mehta, Vijayalakshmi Sridharan, Kirandeep Gill, Sunil Bansal, John B Tyburski, Amrita K Cheema
Of the validated metabolites, 21 were dysregulated in plasma of 1H exposed rats versus sham (0 Gy) (Supplementary Table 2). At the 3-month time point, we observed an increase in the levels of L-carnitine, arginine, LysoPA, N-undecanoyl-L-homoserine lactone, ceramide (d34:1), glycerol trioleate, sphinganine, and sphingosine-1-phosphate (S1P) and a decrease in the levels of SM(24:1), 4-ethoxy-7-methylcoumarin, and 2-methylbutyrylcarnitine. These results are consistent with previously reported findings at equivalent radiation doses in different animal models.28 S1P is generated during the catabolism of complex sphingolipids and has roles in signaling, proliferation, motility, migration, and survival of both normal and malignant cell types.29 S1P may also be generated by the action of autotaxin on sphingophosphorylcholine.