| First Author | Nácher M | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 5 | Pages | 2437-46 |
| PubMed ID | 21457936 | Mgi Jnum | J:171380 |
| Mgi Id | MGI:4949809 | Doi | 10.1016/j.ajpath.2011.01.039 |
| Citation | Nacher M, et al. (2011) Physiological Contribution of CD44 as a Ligand for E-Selectin during Inflammatory T-Cell Recruitment. Am J Pathol 178(5):2437-46 |
| abstractText | Endothelial selectins guide the migration of inflammatory T cells to extralymphoid tissues. Whereas P-selectin glycoprotein ligand-1 (PSGL-1) functions as the exclusive ligand for P-selectin, it acts in coordination with additional glycoproteins to mediate E-selectin binding. CD44 can act as one such ligand in neutrophils, but its contribution in inflammatory T lymphocytes remains unexplored. We have used real-time in vivo imaging of the cremasteric and dermal microcirculations to explore the dynamics of leukocyte recruitment, as well as the physiological contribution of CD44 in a model of Th1-driven inflammation. CD4(+) T-cell rolling frequency and kinetics, as well as arrest, were dependent on endothelial selectins and were markedly altered under inflammatory conditions. CD44 extracted from Th1 cells bound to soluble E-selectin in vitro and cooperated with PSGL-1 by controlling rolling velocities and promoting firm arrest. Using several competitive recruitment assays in a delayed-type hypersensitivity model, we show that the combined absence of CD44 and PSGL-1 impairs inflammatory T-cell recruitment beyond that of PSGL-1 alone. Differential expression of leukocyte fucosyltransferases in these cells may account for the differential use of E-selectin ligands relative to neutrophils. Our results identify additional mechanisms by which CD44 modulates the inflammatory response. |
