In vivo and in vitro differences between leukocytic uptake of oligodeoxynucleotides.
Development and application of therapeutic oligonucleotides rely on proper analysis of binding and uptake. We have used several model oligodeoxynucleotides (ODNs) to analyze binding/uptake by rat and human leukocytes. Here we describe: (1) differences between in vivo and in vitro uptake of ODNs to rat leukocytes, (2) differences after injection of lipopolysaccharide (LPS), (3) large in vitro differences between primary mononuclear cells in PBS, plasma and blood, and (4) differences of ODN uptake between rat and human leukocytes. Our data show that ODN uptake by primary blood cells was different in PBS, plasma and blood. In addition, LPS treatment increased ODN uptake by leukocytes in blood, indicating that pathological conditions may influence ODN uptake. Furthermore, ODN uptake in rat and human blood is also different, suggesting that preclinical ODN uptake data from rat blood cannot easily be extrapolated to the human condition.
Zhang
Z
Z
Institute of Brain Research, University of Tübingen, Calwer Strasse 3, Tübingen, Germany. zhangzhiren@yahoo.com
Zhang
Z-Y
ZY
Schluesener
H J
HJ
D000818:Animals; D002021:Buffers; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007274:Injections, Intraperitoneal; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009841:Oligonucleotides / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew
D002021:Buffers; D008070:Lipopolysaccharides; D009841:Oligonucleotides