Augmentation of pulmonary host defense against pseudomonas by FcγRIIA cDNA transfer to the respiratory epithelium

Stefan Worgall, Petr Bezdicek, Moo Kyung Kim, Jong Gu Park, Ravi Singh, Melpo Christofidou-Solomidou, Alice Prince, Imre Kovesdi, Alan D. Schreiber, Ronald Crystal

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Fcγ 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 FcγRIIA cDNA to-induce expression of the human FcγRIIA receptor. Binding and phagocytosis of opsonized sheep red blood cells (SRBCs) by the A549 human lung epithelial cell line after Ad-mediated FcγRIIA gene transfer was demonstrated using light and fluorescence microscopy and phagocytic assays with 51Cr-labeled SRBCs. When A549 cells were infected with an Ad vector expressing a FcγRIIA 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 FcγRIIA in the lung after intratracheal administration of the AdFcγRIIA enhanced clearance of opsonized Pseudomonas aeruginosa from the lung in normal rats and in mice deficient in Fcγ receptor expression. Similar results were observed with a chimeric FcγRIIA construct containing the extracellular domain of FcγRIIIA. Together, these data demonstrate that Ad-mediated FcyRIIA 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 non- phagocytic cells to clear bacteria or other opsonized particulate antigens from the respiratory tract.

Original languageEnglish
Pages (from-to)409-418
Number of pages10
JournalJournal of Clinical Investigation
Volume104
Issue number4
DOIs
Publication statusPublished - 1 Jan 1999
Externally publishedYes

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Respiratory Mucosa
Pseudomonas
Phagocytosis
Adenoviridae
Phagocytes
Complementary DNA
Antigens
Sheep
Lung
Fc Receptors
Erythrocytes
Immunoglobulin G
Epithelial Cells
Genes
Feasibility Studies
Phenylalanine
Fluorescence Microscopy
Respiratory System
Pseudomonas aeruginosa
Bacteria

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Augmentation of pulmonary host defense against pseudomonas by FcγRIIA cDNA transfer to the respiratory epithelium. / Worgall, Stefan; Bezdicek, Petr; Kim, Moo Kyung; Park, Jong Gu; Singh, Ravi; Christofidou-Solomidou, Melpo; Prince, Alice; Kovesdi, Imre; Schreiber, Alan D.; Crystal, Ronald.

In: Journal of Clinical Investigation, Vol. 104, No. 4, 01.01.1999, p. 409-418.

Research output: Contribution to journalArticle

Worgall, S, Bezdicek, P, Kim, MK, Park, JG, Singh, R, Christofidou-Solomidou, M, Prince, A, Kovesdi, I, Schreiber, AD & Crystal, R 1999, 'Augmentation of pulmonary host defense against pseudomonas by FcγRIIA cDNA transfer to the respiratory epithelium', Journal of Clinical Investigation, vol. 104, no. 4, pp. 409-418. https://doi.org/10.1172/JCI5432
Worgall, Stefan ; Bezdicek, Petr ; Kim, Moo Kyung ; Park, Jong Gu ; Singh, Ravi ; Christofidou-Solomidou, Melpo ; Prince, Alice ; Kovesdi, Imre ; Schreiber, Alan D. ; Crystal, Ronald. / Augmentation of pulmonary host defense against pseudomonas by FcγRIIA cDNA transfer to the respiratory epithelium. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 4. pp. 409-418.
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