Biodistribution of injected tritiated hyaluronic acid in mice: a comparison between macromolecules and hyaluronic acid-derived oligosaccharides.
BACKGROUND
Hyaluronan (HA) has been reported to bind specifically and with high affinity to various cell types and to directly modify cell behaviour. In a previous report we demonstrated that both high molecular weight molecules (HA(H)) and HA-derived oligosaccharides were efficient at triggering terminal differentiation of acute myeloid leukemia (AML) blasts, in vitro, through CD44 ligation.


METHODS
To explore the possibility of using HA for a differentiation therapy in AML, we investigated whether intravenous injection of tritiated HA(H) and/or HA-derived oligosaccharides (HA10-20) into mice accumulated in bone marrow, the main site of AML cell proliferation.


RESULTS
The present work showed that the level of HA in bone marrow: 1) was maximum 5 hours after injection of either HA(H) or HA10-20; 2) was about 40 times higher after HA(H) than after HA10-20 injection. The amount of HA in bone marrow (5.8% ID/g) was two-fold higher than in serum, indicating that it was not due to circulating blood. Finally, using chromatographic analysis, we showed that about 34% of tritiated HA present in bone marrow 5 hours after HA(H) injection displayed a size higher or equal to HA10.


CONCLUSIONS
After a single injection of macromolecular hyaluronan in mouse bone marrow we obtained a concentration of oligosaccharides close to the one shown to trigger AML cell differentiation in vitro. A part of the oligosaccharides had a size higher than or equal to the minimal one required to interact with HA receptors.
Courel
Marie-Noelle
MN
Laboratoire d'Oncologie Moléculaire, Centre Henri-Becquerel, rue d'Amiens, 76000 Rouen, France. mncourel@rouen.fnclcc.fr
Maingonnat
Catherine
C
Bertrand
Philippe
P
Chauzy
Claude
C
Smadja-Joffe
Florence
F
Delpech
Bertrand
B
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009844:Oligosaccharides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014316:Tritium
D009844:Oligosaccharides; D014316:Tritium; D006820:Hyaluronic Acid