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  • Title: Anti-moesin antibodies derived from patients with aplastic anemia stimulate monocytic cells to secrete TNF-alpha through an ERK1/2-dependent pathway.
    Author: Espinoza JL, Takamatsu H, Lu X, Qi Z, Nakao S.
    Journal: Int Immunol; 2009 Aug; 21(8):913-23. PubMed ID: 19556303.
    Abstract:
    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.
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