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International Immunology Advance Access originally published online on June 25, 2009
International Immunology 2009 21(8):913-923; doi:10.1093/intimm/dxp058
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Anti-moesin antibodies derived from patients with aplastic anemia stimulate monocytic cells to secrete TNF-{alpha} through an ERK1/2-dependent pathway

J. Luis Espinoza, Hiroyuki Takamatsu, Xuzhang Lu, Zhirong Qi and Shinji Nakao

Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan

Correspondence to: S. Nakao; E-mail: snakao{at}med3.m.kanazawa-u.ac.jp

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.

Keywords: aplastic anemia, auto-antibody, moesin

Transmitting editor: K. Yamamoto

Received 9 March 2009, accepted 22 May 2009.


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