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

B. Ochietti, P. Lemieux, A. V. Kabanov, S. Vinogradov, Y. St-Pierre, V. Alakhov

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)939-945
Number of pages7
JournalGene Therapy
Volume9
Issue number14
DOIs
StatePublished - Jan 1 2002

Fingerprint

Polyethyleneimine
Neutrophil Infiltration
Intercellular Adhesion Molecule-1
Liver
Plasmids
Cell Adhesion Molecules
DNA
Vascular Endothelium
Transgenes
Chemokines
pluronic block copolymer P123
Neutrophils
Polymerase Chain Reaction
Messenger RNA
Injections
Genes

Keywords

  • Gene therapy
  • ICAM-1
  • Immune response
  • Liver
  • Neutrophil invasion
  • Non-viral gene delivery

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

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. / Ochietti, B.; Lemieux, P.; Kabanov, A. V.; Vinogradov, S.; St-Pierre, Y.; Alakhov, V.

In: Gene Therapy, Vol. 9, No. 14, 01.01.2002, p. 939-945.

Research output: Contribution to journalArticle

Ochietti, B. ; Lemieux, P. ; Kabanov, A. V. ; Vinogradov, S. ; St-Pierre, Y. ; Alakhov, V. / 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. In: Gene Therapy. 2002 ; Vol. 9, No. 14. pp. 939-945.
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