Anti-moesin antibodies derived from patients with aplastic anemia stimulate monocytic cells to secrete TNF-alpha through an ERK1/2-dependent pathway.
Antibodies specific to moesin, which are frequently detectable in the serum of patients with aplastic anemia (AA), can induce tumor necrosis factor-alpha (TNF-alpha) secretion from monocytes and a human monocytic leukemia cell line THP-1. We investigated the mechanisms responsible for TNF-alpha secretion from monocytic cells induced by the auto-antibodies that are purified from the sera of AA patients. TNF-alpha induction by anti-moesin antibodies depended on the amount of cell surface moesin expressed by THP-1 cells. F(ab')(2) fragments prepared from the anti-moesin antibodies were able to stimulate THP-1 cells to secrete TNF-alpha and this stimulatory effect was enhanced by cross-linking of moesins with anti-human IgG F(ab')(2) fragment antibodies. Anti-moesin antibodies as well as their F(ab')(2) fragments induced the phosphorylation of ERK1/2 in monocytic cells and this effect was suppressed by the addition of an ERK1/2 inhibitor. Moreover, anti-moesin antibody treatment induced the phosphorylation of moesin proteins in the monocytes and THP-1 cells within 30 min. These results indicate that anti-moesin antibodies induce TNF-alpha secretion from monocytes through the activation of the ERK1/2 pathway provoked by direct binding to moesin on the cells.
Espinoza
J Luis
JL
Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Takamatsu
Hiroyuki
H
Lu
Xuzhang
X
Qi
Zhirong
Z
Nakao
Shinji
S
D000741:Anemia, Aplastic / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D008840:Microfilament Proteins / Q000276:immunology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D001323:Autoantibodies; D008840:Microfilament Proteins; D014409:Tumor Necrosis Factor-alpha; C071058:moesin; D048052:Mitogen-Activated Protein Kinase 3