HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takamatsu, H. Articles by Nakao, S. Search for Related Content PubMed PubMed Citation Articles by Takamatsu, H. Articles by Nakao, S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Anti-Moesin Antibodies in the Serum of Patients with Aplastic Anemia Stimulate Peripheral Blood Mononuclear Cells to Secrete TNF- and IFN-¹

Hiroyuki Takamatsu^2,*,, J. Luis Espinoza^2,*, Xuzhang Lu^*, Zhirong Qi^*, Katsuya Okawa and Shinji Nakao^3,*

^* Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, and Internal Medicine, NTT WEST Kanazawa Hospital, Kanazawa, Ishikawa, and Biomolecular Characterization Unit, Frontier Technology Center, Kyoto University Graduate School of Medicine, Kyoto, Japan

Moesin is an intracellular protein that links the cell membrane and cytoskeleton, while also mediating the formation of microtubules and cell adhesion sites as well as ruffling of the cell membrane. To determine the roles of anti-moesin Abs derived from the serum of patients with aplastic anemia (AA) in the pathophysiology of bone marrow failure, we studied the expression of moesin on various blood cells and the effects of anti-moesin Abs on the moesin-expressing cells. The proteins recognized by anti-moesin mAbs were detectable on the surface of T cells, NK cells, and monocytes from healthy individuals as well as on THP-1 cells. The peptide mass fingerprinting of the THP-1 cell surface protein and the knock-down experiments using short hairpin RNA proved that the protein is moesin itself. Both the anti-moesin mAbs and the anti-moesin polyclonal Abs purified from the AA patients’ sera stimulated THP-1 cells and the PBMCs of healthy individuals and AA patients to secrete 60–80% as much TNF- as did LPS 100 ng/ml. Although the polyclonal Abs induced IFN- secretion from the PBMCs of healthy individuals only when the PBMCs were prestimulated by anti-CD3 mAbs, the anti-moesin Abs were capable of inducing IFN- secretion from the PBMCs of AA patients by themselves. Anti-moesin Abs may therefore indirectly contribute to the suppression of hematopoiesis in AA patients by inducing myelosuppressive cytokines from immunocompetent cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Technology, Sports and Culture of Japan (KAKENHI No. 19659243) and grants from the Research Committee for Idiopathic Hematopoietic Disorders, the Ministry of Health, Labor, and Welfare, Japan.

² H.T. and J.L.E. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Shinji Nakao, Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan. E-mail address: snakao{at}med3.m.kanazawa-u.ac.jp

⁴ Abbreviations used in this paper: AA, aplastic anemia; BM, bone marrow; pAb, polyclonal Ab; PB, peripheral blood.

This article has been cited by other articles:

				J. L. Espinoza, H. Takamatsu, X. Lu, Z. Qi, and S. Nakao Anti-moesin antibodies derived from patients with aplastic anemia stimulate monocytic cells to secrete TNF-{alpha} through an ERK1/2-dependent pathway Int. Immunol., August 1, 2009; 21(8): 913 - 923. [Abstract] [Full Text] [PDF]