PT - JOURNAL ARTICLE AU - Elisabet Gullberg AU - Åsa V. Keita AU - Sa'ad Y. Salim AU - Margaretha Andersson AU - Karin D. Caldwell AU - Johan D. Söderholm AU - Per Artursson TI - Identification of Cell Adhesion Molecules in the Human Follicle-Associated Epithelium That Improve Nanoparticle Uptake into the Peyer's Patches AID - 10.1124/jpet.106.107847 DP - 2006 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 632--639 VI - 319 IP - 2 4099 - http://jpet.aspetjournals.org/content/319/2/632.short 4100 - http://jpet.aspetjournals.org/content/319/2/632.full SO - J Pharmacol Exp Ther2006 Nov 01; 319 AB - The aim of this study was to identify cell adhesion molecules that could serve as targets of the human follicle-associated epithelium (FAE) overlying Peyer's patches and to assess nanoparticle uptake levels across this epithelium. We first studied the expression of the mouse M-cell marker β1-integrin and used a model of human FAE derived from intestinal epithelial Caco-2 cells and Raji B-cells to identify additional potential targets by cDNA array. The protein expression of potential targets in the model FAE and in human ileal FAE tissues was quantified by immunofluorescence. Integrin targeting was studied by investigating the transport of Arg-Gly-Asp (RGD)-coated (integrin-binding), Arg-Gly-Glu (RGE)-coated (nonintegrin-binding), and uncoated nanoparticles across ileal specimens mounted in Ussing chambers. Both β1-integrin and the cell adhesion molecule CD9 were more abundantly expressed in the model and human FAE compared with the Caco-2 control cells or villus epithelium (VE). Uncoated nanoparticles were not taken up across either FAE or VE. General integrin targeting with RGD improved the nanoparticle transport dramatically across the FAE and to a lower extent across the VE. Compared with RGE, RGD improved transport 4-fold across the FAE. There was no difference in the transport of RGD- and RGE-coated nanoparticles across the VE. In conclusion, β1-integrin and CD9 were identified as targets in human FAE. The difference in RGD- and RGE-mediated transport across the FAE, but not the VE, suggests that a specific integrin interaction was the dominating mechanism for improved nanoparticle uptake across the FAE., whereas charge interaction contributed substantially to the improved VE uptake. The American Society for Pharmacology and Experimental Therapeutics