Sumiko Tanaka

Immunohistochemical study of transferrin receptor expression in the placenta of pre-eclamptic pregnancy

Transport of iron from the mother to the fetus is essential for the normal development of the fetus and abnormalities in the transferrin receptor (TFR) on the placental trophoblasts might have some crucial effects on the fetal iron metabolism. The present study was undertaken to determine whether there are any changes in the expression of the transferrin receptor in the placenta from pre-eclamptic mothers. An immunohistochemical study using antibodies specific for C-terminus and N-terminus regions of the TFR revealed that TFR expression by syncytiotrophoblasts around chorionic villi is markedly reduced in placentae from pre-eclamptic pregnancies compared to those from normal pregnancies and pregnancies at early gestational age that terminated by abortion. The same result, although to a lesser extent, was obtained even in trophoblasts which were located around atrophic villi with fibrotic changes in the interstitium, or which invaded into the deciduas. The expression of human chorionic gonadotropin (HCG) on those cells was observed to the same extent in the normal and pre-eclamptic pregnancy groups. The concentration of TFR in the peripheral blood also decreased in pre-eclampsia. These results suggest that TFR synthesis in the pre-eclampsia, especially in the placental trophoblasts, is decreased.

Effects of released products from platelets on neutrophilic adhesion to endothelial cells and nylon fibers

In this study, the effects of platelet release products (PRPr), ATP, and ADP on the adhesion of human neutrophils to human umbilical vein endothelial cells (HUVEC) and nylon fibers (NF) are described and the implications of various adhesion molecules are considered. Adhesion of neutrophils to HUVEC and NF was increased by PRPr, ATP, and ADP, while their adhesion‐increasing actions were cancelled or considerably repressed by apyrase treatment. When anti‐CD11a or anti‐CD11b was added to neutrophils with PRPr, ATP, or ADP, the adhesion‐increasing action was cancelled or considerably repressed. On the other hand, anti‐ICAM‐1 and anti‐CD35 had no significant effects on this action. The above results indicated that platelets, through ATP and ADP in PRPr, increased the adhesion of neutrophils to endothelial cells and foreign bodies. Although it was suggested that the adhesion‐increasing action was at least partially based on CD11a and CD11b, ICAM‐1 and CD35 had no part in the enhancement of the adhesion.

Effects of D-allose on the endocytic activity of dendritic cells and the subsequent stimulation of T cells.

We examined the effects of a rare sugar, D-allose, which is 6-carbon monosaccharide, on endocytosis and T cell stimulation by dendritic cells (DCs). The endocytosis of BCG-anti-BCG immune complexes by DCs markedly decreased in D-allose-containing medium. Co-culture with T cells (mixed leukocyte reaction, MLR) of DCs, which had been exposed to BCG in D-allose-supplemented medium, induced apoptosis of CD4(+) T cells in a manner dependent on D-allose concentration. After the MLR, DCs cultured in the medium with D-allose expressed less CD40 and more Fas ligands than those cultured without D-allose. It was suggested that the functions of DCs, internalization, processing and the subsequent antigen presentation to T cells, are down-regulated via the action of d-allose.

Transferrin Microheterogeneity in Fetal Blood

Objectives: To investigate the distribution of microheterogeneous subfractions of transferrin in fetal blood and the influence of highly sialylated transferrins on fetal growth. Study Method: Serum transferrin concentrations were determined by a standard turbidimetric assay. Microheterogeneous transferrin subfractions were assessed by crossed immunoisoelectric focusing. Results: In normal term infants, total serum transferrin concentrations and percent distribution of highly sialylated transferrins (≧5-sialo-transferrins) were markedly lower; the percent distributions of hyposialylated transferrins (0- and 1-sialo-transferrins) were apparently higher than those in non-pregnant and pregnant women. There was no significant positive correlation between the serum concentrations of total transferrin or highly sialylated transferrins in infants’ blood and birth weights (r = 0.187, p = 0.582; r = 0.374, p = 0.257, respectively). Conclusion: The transferrin microheterogeneity pattern shifted towards reduced glycosylation and sialylation in addition to a decrease in total transferrin concentration in fetal blood compared to that of non-pregnant and pregnant women. The concentrations of serum total transferrin and the highly sialylated transferrins in fetal blood, if higher than a certain level, did not seem to have any influence on normal fetal growth.

Effects of platelet release products on neutrophilic Fc gamma receptors.

Large and small macromolecular activators of phagocytosis from platelets (l‐MAPP and s‐MAPP, respectively), which function via the neutrophilic Fcy receptors (FcγR) were refined from platelet release products by gel filtration and affinity chromatography with the use of an anti transferrin antibody column and the mechanism of phagocytosis activation was investigated. Flow cytometry revealed that l‐MAPP and s‐MAPP did not increase the expression of neutrophilic FcγRII (CD32) and FcγRIII (CD16) antigens, whereas rosette formation of neutrophils with rabbit IgG‐sensitized sheep erythrocytes (EA) in the presence of anti FcγR antibodies suggested that both MAPPs increase the binding ability of FcγRII. On the other hand, the enhancing effect of l‐MAPP and s‐MAPP on neutrophilic phagocytosis disappeared with the increase in phagocytosis by the phosphate‐buffered saline control neutrophils when they were centrifuged with EA before incubation for phagocytosis. The enhanced phagocytosis, both by the two MAPPs and centrifugation, was canceled by treatment of the neutrophils with anti‐CD32 Fab. The phagocytosis activatory effects of MAPP on neutrophils were canceled by anti‐CD71 monoclonal antibody but not by transferrin. J. Leukoc. Biol. 64: 631–635; 1998.

Multicentric reticulohistiocytosis. Report of a case with electron microscopic studies.

Electron microscopic examination of multicentric reticulohistiocytosis (MR) cells is reported. Most of the cells contained numerous dense bodies which seemed to be lysosomes. Complex interdigitations of the membranes of the adjacent MR cells were distinctive findings. Some of the cells contained myelinated dense bodies in the cytoplasm. Histochemically, the cells were strongly positive for acid phosphatase, alpha‐naphthyl butyrate esterase and lysozyme. From these observations, the majority of MR cells appeared to be proliferations of monocyte/macrophage derived cells. In the synovium, these cells resembled type A synovial cells. Other smaller and fewer cells had many rough endoplasmic reticulum (RER), and these resembled type B synovial cells. In the synovium, MR cells might be formed by proliferation and fusion of synovial cells.

Dendritic cell-like immunoreactivity in the glomerulus of the olfactory bulb and olfactory nerves of mice.

Dendritic cell-like immunoreactivity was examined in the mouse brain. The glomerulus of the olfactory bulb and the olfactory nerves were stained by antibodies against the dendritic cells, NLDC-145 and MIDC-8, while these structures were not stained by antibodies against microglia or macrophages, F4/80, Macl or CD45. Immunoelectron microscopy showed that the immunoreaction for NLDC-145 was localized to the sheath and presynaptic terminals of the olfactory nerves. These findings suggest that the sheath and presynaptic terminals of the primary olfactory nerves have some degree of the antigenicity in common with dendritic cells.

Platelet high-density lipoprotein activates transferrin-derived phagocytosis activators, MAPPs, following thrombin digestion

Macromolecular activators of phagocytosis from platelets (MAPPs), transferrin-derived phagocytosis activators released from platelets, activate leukocytic phagocytosis via Fcγ receptors. It has been found that MAPPs can be prepared using stored platelets or their lysate. Using this artificial MAPP production system, it has been found that they can be produced from precursors (tetrameric and dimeric transferrins) following reaction with a low-molecular-weight (LMW) activator of MAPPs, which is liberated from a high-molecular-weight activator of MAPP (HMW activator) by reaction with thrombin. In this study, the HMW activator in platelet lysate was characterized by assaying phagocytosis of washed neutrophils. In an ultracentrifugation study of the platelet lysate, HMW activator activity was observed in the fraction corresponding to the density of high-density lipoprotein (HDL). The activity was observed in the apolipoproteins obtained from the HDL fraction. Among the apolipoproteins tested only apolipoprotein CIII showed the activity to produce MAPP in vitro. Affinity chromatography of the apolipoproteins from the HDL fraction of the platelet lysate using an anti-apolipoprotein CIII column revealed that the substance that binds with the antibody showed MAPP-forming activity. In a gel filtration study of thrombin-treated apolipoprotein CIII, a peak of LMW activator activity was observed for fractions with a molecular size smaller than that of apolipoprotein CIII. Finally, MAPP-forming activity of HDL obtained from the plasma was examined. MAPP was formed only when delipidized HDL was used. In conclusion, it is suggested that platelet HDL is the HMW activator and that this activation is achieved via apolipoprotein CIII after thrombin reaction in platelets.

High incidence of Langerhans cells in lymph nodes of athymic nude mice: an ultrastructural and morphometric study.

Cervical and axillary lymph nodes of athymic nude mice were compared morphometrically and ultrastructurally with those of normal littermates. The lymph nodes of the nude mice were larger and the volumes of the follicle, paracortex, and medulla of the lymph nodes were all larger. The paracortex of nude mice had few lymphocytes and a large number of interdigitating cells (IDC) and Langerhans cells (Lc). The results suggest that the high incidence of Lc and IDC in the lymph nodes of nude mice is due to cell accumulation and not lymphocyte depletion.

An immunohistochemical study of human platelets using a rabbit antibody against H18‐K24 of apolipoprotein CIII (HATKTAK)

H18‐K24 of human apolipopotein CIII (Apo CIII) (HATKTAK) is an activator of the macromolecular activators of phagocytosis from platelets (MAPPs). Using a rabbit antibody against HATKTAK, we performed an immunohistochemical study of human platelets. Indirect ELISA showed that this antibody reacts with Apo CIII‐derived peptides with a C‐terminal of HATKTAK, but not with Apo CIII. Immunoelectron microscopy revealed that reaction of anti‐HATKTAK antibody occurred in the pseudopods of activated platelets. In blood coagula produced from the peripheral blood and formalin‐fixed after various incubation periods, reaction of this antibody with platelets appeared rapidly with a peak at 3 to 6 h of incubation, and then diminished gradually. Leukocytes in the blood coagula were stained strongly positive. In tissue sections, fresh thrombi and hemorrhages with slight fibrin formation revealed a positive response of platelets to anti‐HATKTAK antibody, whereas older ones with leukocytic infiltration, fibrin formation and organization did not. In addition to platelets, endothelial cells and leukocytes were stained positive by anti‐HATKTAK antibody. All of the positive reactions by anti‐HATKTAK antibody disappeared or diminished by co‐incubation with HATKTAK. In conclusion, the anti‐HATKTAK antibody reveals platelets during the early phase of activation.