Publication Type Academic Article
Authors Worgall S, Bezdicek P, Kim M, Park J, Singh R, Christofidou-Solomidou M, Prince A, Kovesdi I, Schreiber A, Crystal R
Journal J Clin Invest
Volume 104
Issue 4
Pagination 409-18
Date Published 08/01/1999
ISSN 0021-9738
Keywords Gene Transfer Techniques, Lung, Pseudomonas aeruginosa, Receptors, IgG
Abstract Fcgamma receptors on the surface of phagocytic cells bind the Fc region of IgG and mediate binding, phagocytosis, and destruction of particulate antigens opsonized by the antigen-specific IgG molecule. The present study evaluates the feasibility of converting lung epithelial cells into phagocytic cells using adenovirus (Ad) vector-mediated gene transfer of FcgammaRIIA cDNA to induce expression of the human FcgammaRIIA receptor. Binding and phagocytosis of opsonized sheep red blood cells (SRBCs) by the A549 human lung epithelial cell line after Ad-mediated FcgammaRIIA gene transfer was demonstrated using light and fluorescence microscopy and phagocytic assays with (51)Cr-labeled SRBCs. When A549 cells were infected with an Ad vector expressing a FcgammaRIIA mutant in which 2 of 3 cytoplasmic tyrosines have been replaced with phenylalanine, only binding, but not phagocytosis, of opsonized SRBCs was observed. In vivo expression of FcgammaRIIA in the lung after intratracheal administration of the AdFcgammaRIIA enhanced clearance of opsonized Pseudomonas aeruginosa from the lung in normal rats and in mice deficient in Fcgamma receptor expression. Similar results were observed with a chimeric FcgammaRIIA construct containing the extracellular domain of FcgammaRIIIA. Together, these data demonstrate that Ad-mediated FcgammaRIIA receptor cDNA expression can mediate the binding and phagocytosis of opsonized particulate antigens by normally nonphagocytic cells, suggesting that gene-transfer strategies might be used to utilize nonphagocytic cells to clear bacteria or other opsonized particulate antigens from the respiratory tract.
DOI 10.1172/JCI5432
PubMed ID 10449433
PubMed Central ID PMC408520
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