Received for publication May 30, 2006.
Revised August 14, 2006.
Accepted for publication August 15, 2006.

Identification of Cell Adhesion Molecules in the Human Follicle Associated Epithelium (FAE) that improves Nanoparticle Uptake into the Peyer's patches

Abstract

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 ₁-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 the 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 RGD-coated (integrin-binding), RGE-coated (non-integrin-binding) and uncoated nanoparticles across human ileal FAE and Villus Epithelial (VE) specimens mounted in Ussing chambers. Both ₁-integrin and the cell adhesion molecule CD9 were more abundantly expressed in the model and human ileal FAE compared with the Caco-2 control cells or VE. Uncoated nanoparticles were not taken up across either FAE or VE, while general integrin targeting with RGD improved the nanoparticle transport dramatically across the FAE. Compared with RGE, RGD improved transport four- fold across the FAE. RGD also improved nanoparticle transport across the VE, but to the same low extent as RGE. In conclusion, ₁-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, suggest that a specific integrin interaction was the dominating mechanism for improved nanoparticle uptake across the FAE, while charge interaction contributed substantially to the improved VE uptake.

Key words: epithel, integrins, intestine, microarray, targeting, transport