Cationic lipid/DNA complexes induce TNF-alpha secretion in splenic macrophages.
Cationic lipids are widely used as vectors to deliver DNA into mammalian cells in vitro and in vivo. However, cationic lipid/DNA lipoplexes induce an inflammatory response, characterized by pro-inflammatory cytokine secretion, which severely limits their use. The main goal of this work is to identify the organs and the cell type involved in TNF-alpha secretion after lipoplex injection. We determined the kinetics of distribution of the cationic lipid/DNA complex in blood, lung, liver and spleen and quantified the TNF-alpha amount in organ homogenates and in the serum at different points of times. Increase in TNF-alpha production was only observed in the spleen and no significant increase of TNF-alpha production could be observed in the other organs. Fractionation of spleen cells revealed that macrophages were mainly responsible for TNF-alpha secretion. This observation was verified in vivo by using macrophage-removing agents. In conclusion, we show here that the TNF-alpha secreted in the serum after intravenous injection of lipoplexes comes mainly from the splenic macrophages.
Lonez
Caroline
C
Université Libre de Bruxelles, Brussels, Belgium.
Vandenbranden
Michel
M
Elouahabi
Abdelatif
A
Ruysschaert
Jean-Marie
JM
D000818:Animals; D002412:Cations / Q000737:chemistry; D002448:Cell Adhesion; D002469:Cell Separation; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004247:DNA / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D008081:Liposomes / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D002412:Cations; D016207:Cytokines; D008055:Lipids; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D004247:DNA