Galectin-3 inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven rat bone marrow cell proliferation and GM-CSF-induced gene transcription.
The expression of galectin-3 (formerly known as IgE-binding protein or Mac-2) in rat bone marrow (BM) was investigated by FACS, immunocytochemical and immunoblot analysis. The functional significance of rat recombinant galectin-3 on mouse recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven proliferation of macrophage progenitors and gene transcription was further examined. Immunocytochemical analysis of in situ BM sections demonstrated galectin-3 in myelopoietic cells and surrounding stroma, whereas erythropoietic and lymphopoietic environments essentially lacked galectin-3 expression. FACS analysis demonstrated that incubation of freshly isolated BMC with lactose, a competing ligand for galectin-3 binding to glycoconjugates, decreased binding of antigalectin antibodies to cells primarily expressing the myeloid antigen recognized by mAb His-54. Similarly, lectin-mediated binding of exogenous galectin-3 to myeloid lineage cells was also demonstrated. Immunoblot analysis of BM eluates demonstrated galectin-3 both in the extracellular matrix and in a lactose elutable form, bound to the surface of BMC. [3H]Thymidine incorporation studies on BMC cultured in the presence of galectin-3 demonstrated suppression of GM-CSF-induced proliferation by galectin-3. In addition, differential display analysis of immediate early gene expression in BMC cultured in the presence of galectin-3 revealed a 76.2% inhibition of GM-CSF-induced gene transcription by galectin-3 assessed by the number of PCR-fragments generated. Our data suggest a role for galectin-3 in the organization of myelopoietic compartments in rat BM and regulation of the action of growth factors on myelopoietic precursor cells.
Krugluger
W
W
Institute of General and Experimental Pathology, Vienna, Austria.
Frigeri
L G
LG
Lucas
T
T
Schmer
M
M
Förster
O
O
Liu
F T
FT
Boltz-Nitulescu
G
G
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D037502:Galectin 3; D005786:Gene Expression Regulation / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D000943:Antigens, Differentiation; D037502:Galectin 3; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor