Anti-moesin antibodies in the serum of patients with aplastic anemia stimulate peripheral blood mononuclear cells to secrete TNF-alpha and IFN-gamma.
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-alpha as did LPS 100 ng/ml. Although the polyclonal Abs induced IFN-gamma 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-gamma 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.
Takamatsu
Hiroyuki
H
Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.
Espinoza
J Luis
JL
Lu
Xuzhang
X
Qi
Zhirong
Z
Okawa
Katsuya
K
Nakao
Shinji
S
D000741:Anemia, Aplastic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood* / Q000502:physiology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D019169:Jurkat Cells; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020298:U937 Cells
D001323:Autoantibodies; D008840:Microfilament Proteins; D014409:Tumor Necrosis Factor-alpha; C071058:moesin; D007371:Interferon-gamma