Targeted gene delivery to alveolar macrophages via Fc receptor-mediated endocytosis.

摘要: Alveolar macrophage (AM) plays important roles in lung homeostasis and pathogenesis of diseases. The study gene function regulation as well its potential therapeutic intervention will require the development vectors capable safe efficient transfer DNA to AM. In present study, we report a new transfection system that utilizes Fc receptor-mediated endocytosis means target This employs molecular conjugates consisting cognate moiety, this case IgG which recognizes AM receptor, covalently-linked DNA-binding such cationic polyamine. A Complex was formed between immunoglobulin G-polylysine conjugate (IgG-pL) plasmid carrying LacZ reporter (pSV beta). conjugate-DNA complex added directly AMs culture incubated for 24 h, after expression analyzed beta-galactosidase activity by microfluorometry using fluorogenic substrate, 5-dodecanoylaminofluorescein di-beta-D-galactopyranoside (C12FDG). treated with IgG-pL/DNA exhibited galactosidase significantly augmented over background levels. Effective shown both moiety cell surface receptor. Specific internalization receptor pathway verified competitive inhibition excess IgG. Under condition, inhibited, suggesting through mediated pathway. requirement receptors further demonstrated cells lack receptors, e.g., alveolar epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)