title: Physiological contribution of CD44 as a ligand for E-Selectin during inflammatory T-cell recruitment.
abstract: 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.
authors: Department of Epidemiology, Atherothrombosis and Imaging, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors: Maria
authors: M
authors: Nácher
authors: Ana Belén
authors: AB
authors: Blázquez
authors: Bojing
authors: B
authors: Shao
authors: Adela
authors: A
authors: Matesanz
authors: Colette
authors: C
authors: Prophete
authors: M Cecilia
authors: MC
authors: Berin
authors: Paul S
authors: PS
authors: Frenette
authors: Andrés
authors: A
authors: Hidalgo
mesh_terms: D000818:Animals; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*
chemical_list: C476399:Cd44 protein, mouse; D019040:E-Selectin; D018960:Hyaluronan Receptors; D008024:Ligands