ULEX-EUROPAEUS-1 LECTIN TARGETS MICROSPHERES TO MOUSE PEYERS PATCH M-CELLS IN-VIVO

The interaction of Inter microspheres with mouse Peyer's patch membran ous M-cells was studied in a mouse gut loop model after the microspher es were coated with a variety of agents. Carboxylated microspheres (di ameter 0.5 mu m) were covalently coated with lectins Ulex europaeus 1, Concanavalin A, Euonymus europaeus and Bandeiraea simplicifolia 1 iso lectin-B-4, human immunoglobulin A or bovine serum albumin. Of the tre atments examined, only Ulex europaeus (UEA1) resulted in significant s elective binding of microspheres to M-cells. UEA1-coated microspheres bound to M-cells at a level 100-fold greater than BSA-coated microsphe res, but binding to enterocytes was unaffected Incubation of UEA1-coat ed microspheres with chi-L-fucose reduced M-cell binding to a level co mparable with BSA-coated microspheres. This indicated that targeting b y UEA1 was via a carbohydrate receptor on the M-cell surface. Adherenc e of UEA1-coated microspheres to M-cells occurred within 10 min of ino culation into mouse gut loops and UEA1-coated microspheres were transp orted to 10 mu m below the apical surface of M-cells within 60 min of inoculation. UEA1-coated microspheres also targeted mouse Peyer's patc h M-cells after intragastric administration. These results demonstrate d that altering the surface chemistry of carboxylated polystyrene micr ospheres increased M-cell targeting, suggesting a strategy to enhance delivery of vaccine antigens to the mucosal immune system. (C) 1998 El sevier Science Ltd. All rights reserved.