Carbohydrate does not modulate the in vivo effects of injected interleukin-3.
Murine interleukin-3 (IL-3) has extensive N-linked glycosylation. Experiments were performed to determine whether the T cell-derived glycosylated IL-3 differs in its biological activity in vivo when compared with a chemically synthesized form of nonglycosylated IL-3. Groups of mice were treated by intravenous injection with identical units of IL-3 bioactivity as determined in vitro in a cell-proliferation assay. Mice that were treated with seven 5000-unit doses of either form of IL-3, given in 12-hour intervals, showed a small but significant increase in the frequency of mast cell precursor cells in the spleen and of IL-3-responsive colony-forming unit cells (CFU-C). There was no difference in potency of glycosylated and nonglycosylated IL-3. Induction, by IL-3, of histidine decarboxylase in bone marrow and spleen cells was used as a second measure for IL-3 bioactivity. Both IL-3 preparations showed good in vivo histidine decarboxylase inducing activity; however, T cell-derived glycosylated IL-3 was significantly more effective than synthetic IL-3 in inducing the enzyme histidine decarboxylase in bone marrow and in spleen cells. Pharmacokinetic studies showed that chemically synthesized IL-3 was cleared about twice as fast as the T cell-derived IL-3 and that there may be some tissue trapping of glycosylated IL-3. The shorter in vivo half-life of nonglycosylated IL-3 appears to have significant pharmacological consequences on the short-term effect of inducing histidine decarboxylase activity, but not on the effect of the long-term treatment of IL-3 on stimulating the increase of hematopoietic progenitor cells.
Ziltener
H J
HJ
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Clark-Lewis
I
I
Jones
A T
AT
Dy
M
M
D000818:Animals; D002460:Cell Line; D003114:Colony-Forming Units Assay; D004790:Enzyme Induction / Q000187:drug effects; D006031:Glycosylation; D006640:Histidine Decarboxylase / Q000096:biosynthesis; D007377:Interleukin-3 / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008407:Mast Cells / Q000166:cytology*; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology
D007377:Interleukin-3; D006640:Histidine Decarboxylase