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.
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.
Ochietti
B
B
Centre de Recherche en Santé Humaine, INRS-Institut Armand-Frappier, Laval, PQ, Canada.
Lemieux
P
P
Kabanov
A V
AV
Vinogradov
S
S
St-Pierre
Y
Y
Alakhov
V
V
D000818:Animals; D002634:Chemotaxis, Leukocyte; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D007275:Injections, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008107:Liver Diseases / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D010957:Plasmids / Q000008:administration & dosage*; D011060:Poloxalene; D011094:Polyethyleneimine; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; C464484:pluronic block copolymer P123; D011094:Polyethyleneimine; D011060:Poloxalene