A novel mechanism in suppression of erythropoiesis during inflammation: a crucial role of RCAS1.
A novel human tumor-associated antigen, receptor-binding cancer antigen expressed on SiSo cells (RCAS1), induces apoptosis in normal human erythroid progenitor cells, which express putative RCAS1 receptors. In the present study, we investigated a possible role of RCAS1 produced by human peripheral blood monocytes (CD14-positive cells) and monocyte-derived macrophages. RCAS1 was immunohistochemically detected in monocytes as well as macrophages. When macrophages were stimulated with lipopolysaccharide (LPS), the expression of RCAS1 was remarkably enhanced. An increased production of RCAS1 mRNA was observed in LPS-stimulated macrophages by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Soluble RCAS1 molecules were only detected in the culture supernatants obtained from LPS-stimulated macrophages. Moreover, LPS-stimulated macrophages induced cell death of erythroid progenitor cells through RCAS1 production. These results suggest that macrophages may negatively regulate erythropoiesis at least in part through the production of RCAS1 molecules, and this may contribute to the pathogenesis of the anemia seen in patients with inflammatory disorders.
Suehiro
Youko
Y
Division of Clinical Immunology, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
Muta
Koichiro
K
Nakashima
Manabu
M
Abe
Yasunobu
Y
Shiratsuchi
Motoaki
M
Shiokawa
Satoshi
S
Ikuyama
Shoichiro
S
Yoshikawa
Yasuji
Y
Watanabe
Takeshi
T
Nishimura
Junji
J
D015703:Antigens, CD / Q000097:blood; D000951:Antigens, Neoplasm / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D004920:Erythropoiesis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C120762:EBAG9 protein, human; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger