Alveolar macrophages inhibit retrovirus-mediated gene transfer to airway epithelia

Human Gene Therapy
P B McCrayB L Davidson

Abstract

Gene transfer with integrating vectors such as recombinant retrovirus has the potential to correct inherited lung diseases permanently. As a gene therapy target, the pulmonary epithelium presents several challenges to vector delivery in vivo. Many of the host defenses that have evolved to prevent infection from inhaled bacteria or viruses represent potential barriers to gene transfer to the lung. We performed in vitro studies to determine whether two components of the innate immune system of the lung, airway surface fluid and alveolar macrophages, inhibit retroviral gene transfer to airway epithelia. Human alveolar macrophages obtained by bronchoalveolar lavage from normal subjects were left untreated or activated with lipopolysaccharide (LPS) for 3 hr in the presence of subconfluent human bronchial epithelial cells (HBE); than 4 x 10(5) cfu DA-luciferase retrovirus was added. Three days after infection, luciferase activity was measured in cell lysates. When the epithelial cells were co-cultured with LPS-activated macrophages, retroviral gene transfer to HBE cells was reduced by approximately 60%. Nonactivated macrophages decreased the transfection to approximately 55% of control values. In control experiments with either activ...Continue Reading

References

May 20, 1988·Cell·C C ShihJ M Coffin
Apr 1, 1989·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·C FrankenJ H Dijkman
Dec 1, 1986·Journal of Virology·K A DaherR I Lehrer
Jan 1, 1994·American Journal of Respiratory Cell and Molecular Biology·A L CozensD C Gruenert
Sep 1, 1995·Nature Medicine·C Wilson, M A Kay
May 1, 1995·Pharmacology & Therapeutics·T Ganz, R I Lehrer
Apr 1, 1995·American Journal of Respiratory and Critical Care Medicine·T Z KhanD W Riches
Jul 1, 1994·Experimental Lung Research·A DohrmanC Basbaum
Jul 1, 1994·American Journal of Respiratory and Critical Care Medicine·R C Boucher
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·M P KavanaughA D Miller
Sep 14, 1994·Journal of Immunological Methods·N Van Rooijen, A Sanders
Mar 1, 1994·The Journal of Clinical Investigation·T R UlichG F Pierce
Feb 1, 1995·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·F BläuerA Schaffner
Mar 1, 1997·American Journal of Respiratory Cell and Molecular Biology·P B McCray, L Bentley

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Citations

Mar 1, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mayumi OaklandPaul B McCray
Jan 31, 2013·Molecular Therapy. Nucleic Acids·Mayumi OaklandPatrick L Sinn
May 5, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hong Peng JiaPaul B McCray
Aug 2, 2002·American Journal of Respiratory Cell and Molecular Biology·Joseph M Pilewski
Nov 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·M WuW J Martin
May 1, 2007·Clinics in Chest Medicine·Viranuj SueblinvongDaniel J Weiss
Jun 2, 2005·The Journal of Gene Medicine·Tae Woo KimSeo Young Jeong
Apr 24, 2002·Pulmonary Pharmacology & Therapeutics·J VadolasP A Ioannou
May 20, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Namho KimJung Soo Suk
Oct 18, 2011·Bioconjugate Chemistry·Olivia M MerkelThomas Kissel
Aug 6, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Daniel J Weiss
Mar 29, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·V A SlepushkinB L Davidson
Jan 25, 2002·Annals of the New York Academy of Sciences·L G Johnson
May 4, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hong Peng JiaPaul B McCray
Sep 25, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Chhinder P SodhiHongpeng Jia
Feb 20, 2019·Journal of Cardiovascular Development and Disease·Michael G KatzKiyotake Ishikawa
Oct 20, 2000·Clinical Orthopaedics and Related Research·R S GoomerD Amiel

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