Lipocalin 2 functions as a negative regulator of red blood cell production in an autocrine fashion.
Members of the lipocalin protein family are typically small, secreted proteins that possess a variety of functions. Although the physiological role of lipocalin 2 remains to be fully elucidated, a few pivotal functions have recently been reported, e.g., regulation of the apoptosis of leukocytes. Unexpectedly, lipocalin 2 is abundantly expressed in erythroid progenitor cells. An in vitro culture experiment demonstrated that lipocalin 2 induces apoptosis and inhibits differentiation of erythroid progenitor cells. During acute anemia the expression of lipocalin 2 was reduced in erythroid cells by a feedback system. Furthermore, injection of recombinant lipocalin 2 into mice suffering from acute anemia retarded the recovery of red blood cell (RBC) numbers, suggesting the importance of reduced expression of lipocalin 2 for the efficient recovery of RBC numbers. These results indicate that lipocalin 2 suppresses RBC production in an autocrine fashion. Hence, anemia arising from pathological conditions, such as chronic inflammation, might be partly due to increased levels of lipocalin 2 secreted from expanded leukocytes and/or macrophages. Also, anemia arising from malignancies might be partly due to the abundant secretion of lipocalin 2 from tumor cells. Thus, lipocalin 2 may represent an attractive therapeutic target for anemia under certain pathological conditions.
Miharada
Ken-ichi
K
Cell Engineering Division, BioResource Center, RIKEN, Tsukuba, Ibaraki, Japan.
Hiroyama
Takashi
T
Sudo
Kazuhiro
K
Nagasawa
Toshiro
T
Nakamura
Yukio
Y
D000209:Acute-Phase Proteins / Q000502:physiology*; D000818:Animals; D017304:Annexin A5 / Q000737:chemistry; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D002470:Cell Survival; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D007377:Interleukin-3 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D000071068:Lipocalin-2; D054834:Lipocalins; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D015233:Models, Statistical; D015513:Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011990:Receptors, Transferrin / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D014018:Tissue Distribution
D000209:Acute-Phase Proteins; D017304:Annexin A5; D015703:Antigens, CD; C068126:CD71 antigen; D007377:Interleukin-3; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; C071332:Lcn2 protein, mouse; D020169:Caspases