Fc(alpha)/mu receptor is a single gene-family member closely related to polymeric immunoglobulin receptor encoded on Chromosome 1.
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Animals↗
Biomedical subjects
A Shibuya
Publications and source records attributed to A Shibuya.
Molecular cloning and characterization of mouse Tspan-3, a novel member of the tetraspanin superfamily, expressed on resting dendritic cells.
Dendritic cells (DCs) are the most potent antigen-presenting cells and play an essential role for triggering T-cell-mediated immune responses. In search for novel cell surface molecules expressed on DCs involved in T cell priming by representational differential analysis, we identified a mouse homologue of Tspan-3 (mTspan-3), a novel member of the tetraspanin superfamily. The mTspan-3 consists of four hydrophobic, putative transmembrane regions, forming a small and a large extracellular loop, with short intracellular amino and carboxil tails. Although the mTspan-3 is expressed on a variety of immune cell types including resting DCs, its expression on DCs is downregulated during activation induced by cross-linking CD40 with anti-CD40 monoclonal antibody. These results suggest that mTspan-3 may be involved in the function of DCs in association with T cell stimulation.
Amino Acid Sequence↗
Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha.
LIM kinases (LIMK1 and LIMK2) regulate actin cytoskeletal reorganization through cofilin phosphorylation downstream of distinct Rho family GTPases. Pak1 and ROCK, respectively, activate LIMK1 and LIMK2 downstream of Rac and Rho; however, an effector protein kinase for LIMKs downstream of Cdc42 remains to be defined. We now report evidence that LIMK1 and LIMK2 activities toward cofilin phosphorylation are stimulated in cells by the co-expression of myotonic dystrophy kinase-related Cdc42-binding kinase alpha (MRCKalpha), an effector protein kinase of Cdc42. In vitro, MRCKalpha phosphorylated the protein kinase domain of LIM kinases, and the site in LIMK2 phosphorylated by MRCKalpha proved to be threonine 505 within the activation segment. Expression of MRCKalpha induced phosphorylation of actin depolymerizing factor (ADF)/cofilin in cells, whereas MRCKalpha-induced ADF/cofilin phosphorylation was inhibited by the co-expression with the protein kinase-deficient form of LIM kinases. These results indicate that MRCKalpha phosphorylates and activates LIM kinases downstream of Cdc42, which in turn regulates the actin cytoskeletal reorganization through the phosphorylation and inactivation of ADF/cofilin.
Animals↗
A novel Fc receptor for IgA and IgM is expressed on both hematopoietic and non-hematopoietic tissues.
By contrast to well-defined Fc gamma and Fc epsilon receptors, the structural and functional characteristics of Fc mu receptor are unclear. We have recently described a novel mouse Fc receptor, designated Fc alpha/mu receptor, and its human homologue, which bind both IgM and IgA. Here we show that the Fc alpha/mu receptor is expressed on mature, but not immature, B lymphocytes and acquires the ability to bind IgM and IgA antibodies after stimulation of B lymphocytes. Moreover, stimulation with phorbol 12-myristate 13-acetate increased endocytosis of IgM-coated microparticles mediated by the Fc alpha/mu receptor expressed on pro-B cell line Ba/F3 cells. We also show that the Fc alpha/mu receptor is expressed in secondary lymphoid organs, such as lymph node and appendix, kidney and intestine, suggesting an important role of the receptor for immunity in these organs.
Animals↗
Thrombotic thrombocytopenic purpura in autoimmune hepatitis.
A 19-year-old woman presented with clinical manifestations of sudden, fulminant thrombotic thrombocytopenic purpura associated with autoimmune hepatitis and autoimmune thrombocytopenic purpura. Although thrombotic thrombocytopenic purpura may, rarely, be associated with systemic lupus erythematosus and other autoimmune diseases, to our knowledge, the syndrome has never been described in association with autoimmune hepatitis. In this patient, too, the etiology of thrombotic thrombocytopenic purpura associated with autoimmune disease remains elusive. The patient was treated with corticosteroid, which brought about no improvement in her condition, and she died of multiorgan failure. Diagnosis is challenging, but prompt diagnosis is necessary because thrombotic thrombocytopenic purpura is a life-threatening syndrome whose prognosis has been improved significantly by early plasmapheresis treatment.
Adult↗
Increased cell surface expression of C-terminal truncated erythropoietin receptors in polycythemia.
Primary familial and congenital polycythemia (PFCP) is a disorder characterized by an increased number of erythrocytes despite normal blood oxygen pressure and a normal serum erythropoietin (EPO) level. Recent studies revealed that erythroid progenitor cells from certain individuals with PFCP express various forms of EPO receptor (EPOR) truncated at the terminal carboxyl site (EPOR-TTC(PFCP)). EPOR-TTC(PFCP) can transmit EPO-mediated proliferative signals more efficiently than can full-length EPOR (EPOR-F), at least partly because of defective recruitment of SHP-1 phosphatase to these receptors. In agreement with previous studies, Ba/F3 transfectants expressing EPOR-TTC(PFCP) showed higher proliferative responses to EPO. In those transfectants, we found that EPOR-TTC(PFCP) was expressed more abundantly on the cell surface than was EPOR-F. This tendency was confirmed by a transient-expression experiment using COS7 cells. Since expression levels of EPOR protein were not significantly different among these transfectants, differences in cell surface expression were likely dependent on post-translational mechanism(s). In addition to defective recruitment of SHP-1 to EPOR-TTC(PFCP), more efficient transport and expression on the cell surface appear to serve as mechanisms responsible for increased EPO-responsiveness of erythroid progenitor cells in PFCP.
Amino Acid Sequence↗
Killer T-cell induction in patients with blastic natural killer cell lymphoma/leukaemia: implications for successful treatment and possible therapeutic strategies.
A rare form of putative natural killer (NK) cell lymphoma called blastic NK cell lymphoma appears to be clinicopathologically distinctive in showing a homogenous lymphoblast, variable expression of CD2, CD4, CD56 and TdT, negative for surface CD3, T-cell receptor antigen, CD16, CD34 and lack of association with Epstein-Barr virus (EBV). We report two patients with blastic NK cell lymphoma and describe the interesting clinical studies. The patients presented with cutaneous plaques. Both patients had adenopathy, and one had marrow involvement at presentation. Unlike in many NK and NK-like T-cell disorders, azurophilic cytoplasmic granules were absent. They expressed intermediate density CD45. In addition, the cells were positive for HLA-DR, CD2, CD4, CD56 and TdT, and negative for EBV transcripts. In spite of the advanced clinical stage, complete remission was achieved by conventional chemotherapy. After interleukin 2 expansion of tumour-infiltrating bone marrow and lymph node cells from the patients, cytotoxic T-cell lines with rearranged T-cell receptor genes were established. They showed specific killing activity against autologous tumour cells in an MHC-restricted fashion, with possible implications for treatment. In addition, upon cessation of maintenance chemotherapy, one patient developed overt leukaemia with blasts expressing CD33 antigens, suggesting a continuous spectrum of blastic NK cell lymphoma to myeloid/NK cell precursor acute leukaemia.
Aged↗
Hepatopulmonary syndrome associated with autoimmune liver cirrhosis.
A 46-year-old woman presented for evaluation of liver dysfunction and dyspnoea. Laboratory examination showed high levels of gamma-globulin, immunoglobulin (Ig)G, and antinuclear antibodies. Laparoscopy demonstrated hepatic cirrhosis. Despite normal spirometry, hypoxaemia (which was worse in standing position) and a low diffusing capacity were present. The shunt ratio calculated using arterial blood gas was 6.4%, but was 40% when measured using 99mTc-macroaggregated albumin scanning. The discrepancy between the ratios indicated that hypoxaemia was caused by intrapulmonary vascular dilatation. The patient was diagnosed with hepatopulmonary syndrome associated with autoimmune liver cirrhosis.
Female↗
Successful donor lymphocyte infusion in a patient with relapse of lymphoblastic leukemia after bone marrow transplantation.
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Adolescent↗
Childhood hypoplastic anemia with sugar chain anomaly of red cell membranes.
BACKGROUND: Childhood hypoplastic anemia of unknown etiology had not existed until now. To assess pathophysiological differentiation in childhood hypoplastic anemia, we analyzed red cell membrane components in six children with hypoplastic anemia of unknown etiology. METHODS: The six children all had chronic moderate anemia and thrombocytopenia. They also showed hypoplastic marrow cellularity with erythroblastopenia, megakaryocytopenia, and mild morphological anomalies (pelger Hëut anomaly of neutrophils and bi- or trinuclear erythroblasts), except for one child who had normal platelets and megakaryocytes. Red blood cells of patients and several anemic children, cord blood and healthy controls were analyzed by the peanut lectin agglutination (PNA) test, flow cytometry, sodium dodecyl sulfate_polyacrylamide gel electrophoresis of membrane proteins, high performance liquid chromatography (HPLC) of sugar chains and the colony-forming assay of bone marrow erythroblasts. RESULTS: In the six children, the PNA agglutination test showed a persistent positive reaction not only for peripheral red blood cells but also for bone marrow erythroblasts. This was not observed in other anemic children and healthy controls. With HPLC analysis, the sugar chains of red blood cell membranes showed the loss of sialic acid from O-linked oligosaccharides. CONCLUSIONS: Our results suggested that the abnormality of red blood cells from these patients was attributable to abnormal surface sugar chains (loss of sialic acid from O-glycan), which are already present at the erythroblast stage in the bone marrow and that may be responsible for a group of anemias.
Anemia, Aplastic↗
Transfusion transmitted virus infection in patients on maintenance haemodialysis and in hospital workers.
A newly discovered DNA virus, transfusion transmitted virus (TTV), was isolated from a post-transfusional hepatitis patient in Japan. A high prevalence (32-46%) of TTV infections in patients receiving maintenance haemodialysis (HD) has been reported but the occupational risk of TTV on HD units has not yet been determined. We determined the prevalence of TTV in workers in the same HD unit and the risk factors for TTV infection in HD patients, using logistic regression analysis. The prevalence of TTV DNA was 59.6% in 198 HD patients, significantly higher than that in the HD unit (13 of 39, 33.3%;P= 0.002) and non-HD healthcare workers (20 of 75, 26.7%; P= 0.001). A logistic regression analysis showed that male gender and negative test results for hepatitis G virus RNA were risk factors for TTV infection, but prior blood transfusion and duration of HD were not. Stepwise selection of multiple regression analysis showed that the presence of hepatitis C virus RNA was the only significant predictor for high serum ALT activity, and that the presence of TTV DNA was not. These results indicate that TTV is one of the prevalent human viruses transmissible either parenterally or nonparenterally in HD patients, but the occupational risk of TTV infection in HD unit workers is as low as in other healthcare workers. The pathogenic effects of TTV on the liver appear to be limited.
Adult↗
[Hepatocellular carcinoma accompanied with primary biliary cirrhosis].
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Age Factors↗
[Embolization of the bilateral internal pudendal arteries for intractable priapism in a child with chronic myelogenous leukemia].
Priapism is an uncommon clinical symptom in children with chronic myelogenous leukemia (CML). Here we report a 14-year-old boy with this symptom, which had appeared 4 days prior to hospitalization. Peripheral blood examination revealed a leukocyte count of 510,000/microliter, (87% neutrophils, 3% eosinophils, 6% basophils, and 1.6% lymphocytes), a hemoglobin level of 6.5 g/dl and a platelet count of 640,000/microliter. Karyotype analysis revealed the Ph1 chromosome and myeloid hyperplasia in the bone marrow. The patient was diagnosed as having chronic myelogenous leukemia (CML) complicated by priapism. In an unsuccessful attempt to alleviate and improve the priapism, urokinase was injected and hydroxyurea was administered for the CML. Angiography confirmed the presence of venous return from the scrotum, and embolization of the bilateral internal pudendal arteries was performed to reduce the amount of inflow. Although this relieved the patient of his pain and prevented penile necrosis, the patient's future sexual potency was sacrificed. Selective embolization of the pudendal arteries can be one of the most effective ways of treating intractable priapism, if angiography confirms the presence of venous return from the penis.
Adolescent↗
Serological analysis of BALB/C methylcholanthrene sarcoma Meth A by SEREX: identification of a cancer/testis antigen.
Antigens of BALB/c methylcholanthrene-induced fibrosarcoma Meth A recognized by the host humoral immune response were investigated by serological analysis of antigens by recombinant expression cloning (SEREX). Immunoscreening a cDNA library from Meth A (Kgamma) cells (Meth A retrovirally transfected with murine IFN-gamma cDNA) with sera from BALB/c mice growing parental Meth A transplants identified 10 antigens. One of them, OY-MS-4, showed characteristics of a cancer/testis (CT) antigen. Nucleotide sequence analysis revealed that OY-MS-4 was identical to a mouse placenta and embryonic expression gene (pem) known to be selectively expressed during embryogenesis and in transformed cell lines. In adult mice, expression of OY-MS-4 was restricted to testis and placenta. Four of 6 methylcholanthrene-induced fibrosarcomas in BALB/c mice showed strong expression of OY-MS-4. In 6 T-cell leukemias, only a dimethylbenzanthracene-induced leukemia, EL4 (C57BL), showed strong expression. Two other tumors, A20.2J and P815, induced by ethylnitrosourea and methylcholanthrene, respectively, also strongly expressed OY-MS-4. The other 9 gene products identified in Meth A by SEREX were expressed in all 15 tumors tested and in a range of normal tissues. Sequence analysis of cDNA inserts coding for the SEREX-defined antigens showed no evidence of mutation. Despite the expression of OY-MS-1-10 antigens in methylcholanthrene sarcomas other than Meth A, no antibody was detected in the sera of mice bearing these other sarcomas. The basis for the unique immunogenicity of OY-MS-1-10 presented by Meth A, but not by other syngeneic tumors expressing these gene products, is unknown.
Amino Acid Sequence↗
Primary structure of human hepatocellular carcinoma-associated aldehyde dehydrogenase.
Tumor-associated aldehyde dehydrogenase (T-ALDH) is strongly expressed in hepatocellular carcinoma (HCC) but undetectable in normal liver. In the present study, this enzyme from human HCC, HCC T-ALDH, was purified and the partial amino acid sequences (384 residues) determined by direct protein sequencing matched the amino acid sequence (453 residues) deduced from cloned HCC T-ALDH cDNAs with an open reading frame. The coding sequences of HCC T-ALDH cDNA, human stomach ALDH3A1 cDNA [Hsu et al., J. Biol. Chem. 267 (1992) 3030-3037] and human squamous cell carcinoma (SCC) T-ALDH cDNA (Schuuring et al., GenBank I.D. M74542) matched one another except for discrepancies at four positions, with consequent P12R, I27F and S134A substitutions. R and A were found in HCC and SCC T-ALDHs, whereas P and S were present in stomach ALDH3A1. To confirm that these discrepancies would have general occurrence, coding sequences of HCC T-ALDH cDNAs from six patients and stomach ALDH3A1 cDNAs from two individuals were examined and all were found to encode ALDH3A1 having R, I and A at protein positions 12, 27 and 134, respectively, indicating HCC T-ALDH to be variant ALDH3A1 which is common in human stomach tissues.
Aldehyde Dehydrogenase↗
Molecular cloning and chromosomal mapping of a novel five-span transmembrane protein gene, M83.
In an attempt to identify novel transmembrane molecules expressed on hematopoietic cells, we identified a novel transmembrane protein gene, M83. Cloning of the full-length cDNAs of human and mouse M83 revealed that M83 encodes a type I transmembrane protein with a region containing five hydrophobic segments within the C-terminal part of the protein, suggesting that M83 is a five-span transmembrane molecule. The M83 protein was expressed on the cell surface as a glycosylated protein with a molecular mass of 84 kDa. The M83 gene was localized to human chromosome 16p13.3, mouse chromosome 17B1, and rat chromosome 10q12.3 distal. In human, M83 mRNA was highly expressed in placenta, pancreas, and lymphohematopoietic tissues including peripheral blood, spleen, and bone marrow. Among hematopoietic cells, it was highly expressed in resting T lymphocytes and was downregulated by cell activation, suggestive of its biological role related to the T cell resting status.
Amino Acid Sequence↗
Molecular cloning and characterization of CRLM-2, a novel type I cytokine receptor preferentially expressed in hematopoietic cells.
A murine expressed sequence tag (EST) showing homology with erythropoietin receptor (EPOR) was identified in the EST database. Cloning of the full-length cDNA revealed a 359 amino acid novel type I cytokine receptor, designated cytokine receptor like molecule-2 (CRLM-2). While CRLM-2 lacks typical WSXWS motif, it has a significant homology with EPOR, IL-2 receptor beta and gamma, and IL-9 receptor alpha. The murine CRLM-2 gene is composed of 8 exons, and an alternative mRNA splicing generates a variant transcript encoding a soluble CRLM-2. CRLM-2 is preferentially expressed in hematopoietic cells, particularly in hematopoietic progenitors and myeloid cells. Furthermore, CRLM-2 is constitutively associated with JAK2, a well-known tyrosine kinase that transmits signals from cytokine receptors. These data strongly suggest that CRLM-2 is a novel cytokine receptor involved in the regulation of hematopoietic system.
Alternative Splicing↗
Dominant expansion of human T cells in non-obese diabetic/severe combined immunodeficiency mice implanted with human bone fragments.
OBJECTIVE: To establish an in vivo animal model in which human T cells develop and function normally, a step toward developing new vaccines or chemical compounds that modulate immune functions and toward understanding T-cell immunity in humans. MATERIALS AND METHODS: Human bone fragments were implanted into non-obese diabetes/severe combined immunodeficiency (NOD/SCID) mice. The presence of human blood cells in the peripheral blood of these mice was monitored periodically by immunostaining and fluorescence-activated cell sorting. RESULTS: After implantation of bone fragments, dominant expansion of human T lymphocytes, rather than myeloid and B cells, was observed over a 3-month period. In some cases, the proportion of human T cells rose to 40% of the peripheral blood mononuclear cells. These T cells showed CD4/CD8 ratios similar to those observed in human peripheral blood lymphocytes and had a broad repertoire of rearranged T-cell receptor genes. Graft-versus-host reaction was not noted in any organ analyzed. To assess the suitability of NOD/SCID mice implanted with human bone fragments (hu-bone-NOD/SCID mice) as an in vivo model for HIV infection, the mice were infected with a T-lymphotropic strain of HIV-1 (NL4-3) at 7 weeks posttransplant. Serum p24 gag was detected at 2 weeks after inoculation, after which total CD4-positive cell numbers declined, as seen clinically in patients infected with HIV. CONCLUSION: Although the precise mechanism is yet to be determined by which predominant expansion of human T cells occurs in hu-bone-NOD/SCID mice, such mice appear likely to serve as a useful and versatile model for studies involving human T-cell immunity.
Animals↗