EFFECTS OF POLYETHYLENEIMINE ON ENDOCYTOSIS AND LYSOSOME STABILITY

Polyethyleneimine (PEI) is shown to destabilize isolated rat liver lys osomes, as indicated by a decrease in the latency of their acid N-acet yl-beta-glucosaminidase. PEI also inhibited the generation of radiolab eled digestion products from I-125-labeled bovine serum albumin endocy tosed by rat visceral yolk sac in vitro. However, PEI did not greatly inhibit the endocytic uptake of a nondigestible fluid-phase substrate, fluorescein isothiocyanate (FITC)-dextran. It is hypothesized that PE I inhibits the adsorptive endocytosis of I-125-labeled bovine serum al bumin, and thus its subsequent intralysosomal digestion, by competing with and displacing the labeled protein from its binding sites on the visceral yolk sac cell surface. This hypothesis suggests a plausible e xplanation for the ability of PEI to act as an efficient vector for ge ne and oligonucleotide transfer into mammalian cells. PEI present in t he culture medium is carried into cells by adsorptive endocytosis. Con centrated thus on the endosome membrane, it permeabilizes this membran e and so affords DNA conjugated to the PEI an otherwise unavailable mo de of access into the cytoplasm. BIOCHEM PHARMACOL 56;1:41-46, 1998. ( C) 1998 Elsevier Science Inc.