Lipocalin 2-mediated growth suppression is evident in human erythroid and monocyte/macrophage lineage cells.
Lipocalin 2 (LCN2), a secreted protein of the lipocalin family, induces apoptosis in some types of cells and inhibits bacterial growth by sequestration of the iron-laden bacterial siderophore. We have recently reported that LCN2 inhibits the production of red blood cells in the mouse. Here we analyzed the role of LCN2 in human hematopoiesis. Expression of LCN2 was observed not only in mature cells such as those of the granulocyte/macrophage and erythroid lineages but also in hematopoietic stem/progenitor cells. We also examined expression of two candidate receptors for LCN2, brain type organic cation transporter (BOCT) and megalin, in various cell types. BOCT showed relatively high levels of expression in erythroid and hematopoietic stem/progenitor cells but lower levels in granulocyte/macrophage and T lymphoid cells. Megalin was expressed at high levels in T lymphoid and erythroid cells but at lower levels in granulocyte/macrophage lineage cells. LCN2 suppressed the growth of erythroid and monocyte/macrophage lineages in vitro, but did not have this effect on cells of other lineages. In addition, immature hematopoietic stem/progenitor cells were not sensitive to LCN2. These results demonstrate a lineage-specific role for LCN2 in human hematopoiesis that is reminiscent of its effects upon mouse hematopoiesis and strongly suggest an important in vivo function of LCN2 in the regulation of human hematopoiesis.
Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan.
Kenichi
K
Miharada
Takashi
T
Hiroyama
Kazuhiro
K
Sudo
Inaho
I
Danjo
Toshiro
T
Nagasawa
Yukio
Y
Nakamura
D000209:Acute-Phase Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019070:Cell Lineage; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006098:Granulocytes / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D027701:Organic Cation Transport Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C518841:SLC22A17 protein, human