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Inducing neutrophil recruitment in the liver of ICAM-1-deficient mice using polyethyleneimine grafted with Pluronic P123 as an organ-specific carrier for transgenic ICAM-1

Gene Therapy volume 9, pages 939–945 (2002)Cite this article

Abstract

Coordinated expression of cell adhesion molecules and chemokines on the surface of vascular endothelium is responsible for the homing of immune effector cells to targeted sites. One way to attract non-activated immune cells to targeted organs is to use transgenically expressed adhesion molecules responsible for leukocyte recruitment. We have previously shown that polyethyleneimine (PEI) grafted with non-ionic amphiphilic Pluronic P123 block copolymer (P123PEI) modifies biodistribution of plasmid DNA toward the liver. In the present study, a P123PEI-formulated plasmid carrying the gene encoding for the murine ICAM-1 molecule was injected i.v. into transgenic ICAM-1-deficient mice. The RT-PCR analysis of ICAM-1 mRNA expression showed that P123PEI induced a dose-dependent expression of ICAM-1 in the liver. Furthermore, this expression of ICAM-1 induced neutrophil invasion in the liver, while no such invasion was observed in mice injected with formulated control plasmid or naked DNA. These results suggest that P123PEI allows functional transgene expression in the liver following i.v. injection and that ICAM-1 could be used to enhance immune response locally by attracting immune effector cells.

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Acknowledgements

We gratefully acknowledge the technical assistance of Claire Beauchemin and Doris Legault. The support from the National Science Foundation (BES-9907281) and Nebraska Research Initiative (Gene Therapy) is essential for the studies on non-viral gene delivery systems in UNMC. Dr St-Pierre is a scholar of the Fonds de la Recherche en Santé du Québec.

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Authors and Affiliations

  1. Centre de Recherche en Santé Humaine, INRS-Institut Armand-Frappier, Laval, PQ, Canada

    B Ochietti & Y St-Pierre

  2. Supratek Pharma, Laval, PQ, Canada

    P Lemieux & V Alakhov

  3. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

    AV Kabanov & S Vinogradov

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  1. B Ochietti
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  2. P Lemieux
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Ochietti, B., Lemieux, P., Kabanov, A. et al. Inducing neutrophil recruitment in the liver of ICAM-1-deficient mice using polyethyleneimine grafted with Pluronic P123 as an organ-specific carrier for transgenic ICAM-1. Gene Ther 9, 939–945 (2002). https://doi.org/10.1038/sj.gt.3301716

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