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Hiroto Ishikura

Publications and source records attributed to Hiroto Ishikura.

6 recordsLinked to original sources
PubMed2005

Immortalized human microglial cell line: phenotypic expression.

Microglia are a major neuroglial component of the CNS, playing an important role as resident immunocompetent and phagocytic cells in the CNS in the event of injury and disease. To understand the role of microglia in the CNS in health and diseases, we have recently established an immortalized clonal cell line of human microglia, HMO6, from human embryonic telencephalon tissue by using a retroviral vector encoding v-myc. This immortalized microglia HMO6 cell line exhibits cell-type-specific antigens for microglia, including CD11b (Mac-1), CD68, CD86 (B7-2), HLA-ABC, HLA-DR, and RCA-1 lectin, and actively phagocytoses latex beads.

Animals↗
PubMed2004

Autoimmune-associated hemophagocytic syndrome.

Hemophagocytic syndrome (HPS) is a clinicopathological condition characterized by the activation of histiocytes with prominent hemophagocytosis in bone marrow and other reticuloendothelial systems. The occurrence of HPS is usually associated with underlying disorders such as infection and lymphoma. Recently, we described patients with autoimmune disease who developed HPS. In these cases there was no evidence of underlying infection and malignancy, and the occurrences of HPS were associated with active autoimmune disease. Based on these observations, we described autoimmune-associated hemophagocytic syndrome (AAHS). This disease entity is becoming better known, and case reports presenting features compatible with clinical AAHS are increasing. Here, we review the clinical aspects, mechanisms, diagnosis, and treatment of AAHS according to our data and that in the literature.

Journal Article↗
PubMed2003

Activation of protein kinase C enhances TNF-alpha-induced differentiation by preventing apoptosis via rapid up-regulation of c-Myc protein expression in HL-60 cells.

Tumor necrosis factor-alpha (TNF-alpha) induces both rapid onset of apoptosis and monocytic differentiation in HL-60 human myeloid leukemia cells. In this study, we examined the effect of activation of protein kinase C (PKC) in c-Myc protein expression in association with the induction of apoptosis and differentiation in TNF-alpha-treated HL-60 cells. Pretreatment with phorbol 12-myristate 13-acetate (PMA), an activator of PKC, prevented TNF-alpha-induced rapid onset of apoptosis, which occurs at 3 h culture with TNF-alpha, concomitantly with the up-regulation of c-Myc protein expression. In addition, PMA enhanced TNF-a-induced differentiation at 24h treatment. This was documented by the expression of integrin Mac-1 molecule (CD11b) on the cell surface and the cellular adhesion to the plastic bottom of the flask, indicating the differentiation along with the monocyte/macrophage lineage. These results indicate that activation of PKC not only counteracts apoptosis but also enhances differentiation in TNF-alpha-treated HL-60 cells. Up-regulation of c-Myc protein evoked by pretreatment with PMA for a short time could disturb the signaling pathway of the ceramide and sphingosine, which are known to function as the endogenous modulators mediating the apoptotic signal of TNF-alpha. Our results strongly suggest the role of c-Myc protein as a mediator of cytoprotective effect of PKC pathway, and PKC pathway opposes apoptosis and consequently undergo differentiation via rapid up-regulated c-Myc protein expression during TNF-alpha signaling of HL-60 cells. Our findings provide a new insight for a role of PKC and c-Myc protein with special reference to the regulatory mechanisms in the decision of cellular fate, differentiation or apoptosis.

Apoptosis↗
PubMed2003

Phagocytosis of terminally differentiated acute promyelocytic leukemia cells by marrow histiocytes during treatment with all-trans retinoic acid.

It has been established that acute promyelocytic leukemia (APL) cells are induced to terminally differentiate by all-trans retinoic acid (ATRA), however, the clearance of differentiated APL cells in vivo has not been well understood. Here, we documented the elimination of terminally differentiated APL cells by histiocytes in bone marrow during differentiation induction therapy. In two ATRA-treated APL patients, bone marrow showed the striking phagocytosis of differentiated APL cells by histiocytes just before the achievement of complete remission. Histiocytes phagocytosed APL cells at the terminal stage of differentiation prior to the late apoptotic event of cell lysis. Engulfed APL cells then undergo morphological features of late apoptosis and finally fragmentation in the cytoplasm of histiocytes. This swift and efficient elimination of APL cells undergoing apoptosis by the histiocytes in bone marrow may be possible pathway, at least partially, for the clearance of differentiated APL cells.

Aged↗