Augmentation of pulmonary host defense against Pseudomonas by FcgammaRIIA cDNA transfer to the respiratory epithelium. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Line
  • DNA, Complementary
  • Epithelial Cells
  • Erythrocytes
  • Humans
  • Mice
  • Opsonin Proteins
  • Phagocytes
  • Phagocytosis
  • Rats
  • Sheep

MeSH Major

  • 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.

publication date

  • August 1999

has subject area

  • Animals
  • Cell Line
  • DNA, Complementary
  • Epithelial Cells
  • Erythrocytes
  • Gene Transfer Techniques
  • Humans
  • Lung
  • Mice
  • Opsonin Proteins
  • Phagocytes
  • Phagocytosis
  • Pseudomonas aeruginosa
  • Rats
  • Receptors, IgG
  • Sheep

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC408520

Digital Object Identifier (DOI)

  • 10.1172/JCI5432

PubMed ID

  • 10449433

Additional Document Info

start page

  • 409

end page

  • 418

volume

  • 104

number

  • 4