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Biomedical subjects

K Ishizaka

Publications and source records attributed to K Ishizaka.

At least 19 recordsLinked to original sources
PubMed1979

Induction of calcium flux across the rat mast cell membrane by bridging IgE receptors.

Rabbit antibody against IgE receptors or its F(ab')2 fragments induced an increase of 45Ca uptake into normal mast cells, and this process was accompanied by histamine release. Evidence was obtained that a substantial portion of 45Ca uptake was due to movement of calcium across the cell membrane. Neither 45Ca uptake nor histamine release was induced by Fab' monomer fragments of the antireceptor antibody. However, bridging of receptor-bound Fab' fragments by antirabbit IgG or bridging of receptor-bound IgE by anti-IgE induced an increase in 45Ca uptake. The results collectively indicate that crosslinking IgE receptors increases the membrane permeability of the mast cells toward calcium.

Animals↗
PubMed1979

Lymphocytes bearing Fc receptors for IgE. II. Induction of Fcepsilon-receptor bearing rat lymphocytes by IgE.

The proportion of lymphocytes bearing receptors for IgE (FcepsilonR) markedly increased after infection of rats with Nippostrongylus brasiliensis (Nb). The FcepsilonR-bearing lymphocytes from the infected animals bound more IgE-coated erythrocytes in rosette assay than FcepsilonR-bearing cells from normal rats, suggesting that the number of FcepsilonR per cell may also increase following the infection. In contrast, the number of IgE-receptors on peritoneal mast cells did not change after Nb infection. The increase in the proportion of FcepsilonR-bearing lymphocytes in Nb-infected rats is probably due to an increased concentration of IgE in the environment. The proportion of FcepsilonR-bearing cells in normal rat lymphocyte suspensions increased by culture of the cells with rat IgE of 1 microgram/ml or higher concentration. Other immunoglobulins such as rat IgG, human IgE, or rabbit IgG failed to induce either FcepsilonR-bearing cells or FcgammaR-bearing cells. It was also found that induction of Fc receptors by rat IgE is confined to FcepsilonR. Kinetic studies on the induction of FcepsilonR-bearing lymphocytes in vitro showed that the proportion of these cells in lymphocyte suspensions increased within 8 hr incubation with rat IgE but not within 4 hr. Evidence was obtained that both RNA synthesis and protein synthesis, but no DNA synthesis, are required for the induction of FcepsilonR-bearing cells or the expression of the receptors on the cell surface.

Animals↗
PubMed1979

Demonstration of Fcgamma receptors on human basophil granulocytes.

Fcgamma receptors were detected on human basophil granulocytes. The mononuclear cell fraction of human peripheral blood was incubated with heat-aggregated human IgG (HGG) followed by 125I-anti-HGG. Autoradiography of the cells showed that the majority of basophil granulocytes gave a significant number of grains. Basophils were not labeled by preincubation of the same cells with monomeric HGG followed by 125I-anti-HGG. However, the binding of aggregated HGG to basophils was inhibited by the presence of a high concentration of monomeric HGG or its Fc fragment but not by the Fab fragment. Evidence was obtained that Fcgamma receptors are distinct from IgE receptors on the same cells: i) Saturation of basophils with IgE did not affect the binding of aggregated HGG to the cells. ii) Preincubation with and the presence of aggregated HGG failed to affect the binding of 125I-IgE to basophils, or to block passive sensitization of the cells with IgE antibodies. iii) The Fcgamma receptors did not co-cap with IgE receptors. Aggregated HGG failed to induce histamine release from basophils even in the presence of D2O. It was also found that the presence of aggregated HGG on basophils did not modulate IgE-mediated histamine release from the cells.

Basophils↗
PubMed1978

Mechanisms of reaginic hypersensitivity and immunotherapy.

Reaginic antibodies in hay fever patients belong to IgE. The immunoglobulin sensitizes basophilic granulocytes and mast cells from homologous species and mediates the release of chemical mediators which cause allergic symptoms. The sensitization is due to the binding of IgE to receptors on the target cells through the Fc portion of the molecules. High affinity of the molecules for the receptor is responsible for the biologic activity of IgE antibodies and for the persistence of sensitization with the antibodies. The initial step of the reaginic hypersensitivity reactions is bridging of cell-bound IgE antibody molecules by a multivalent antigen. Since IgE is firmly bound with receptors, cross-linkage of IgE molecules will cause a disturbance of membrane structure and/or interaction between receptor molecules at the cell membrane, which will activate membrane-associated enzymes. It appears that the activation of sequences of enzymes will lead to the release of chemical mediators from the cells. In view of the role of IgE antibodies in allergic diseases such as hay fever, attempts were made to depress the IgE antibody response to allergen. A experimental model in the mouse indicated that the generation of antigen-specific suppressor T cells is involved in the depression of IgE antibody formation by immunotherapy.

Animals↗
PubMed1978

A new concept of triggering mechanisms of IgE-mediated histamine release.

It is generally accepted that an initial step of reaginic hypersensitivity reactions is a bridging of mast cell--bound IgE antibody molecules by antigen. Since IgE molecules are firmly bound to receptors on mast cells, bridging of cell-bound IgE molecules probably brings receptor molecules into close proximity. A hypothesis was therefore presented that such a local change in membrane structure and/or possible interaction between adjacent receptor molecules may be triggering mechanisms of IgE-mediated histamine release. The hypothesis was tested by use of antibodies against "exposed portion" of receptor molecules on rat basophilic leukemia cells. It was found that antireceptor antibodies and its F(ab')2fragments induced noncytotoxic histamine release from normal rat mast cells without participation of IgE, while the monovalent Fab' fragments of the antibody failed to do so. However, sensitization of normal rat skin with the Fab' fragments followed by an intravenous injection of antirabbit IgG induced skin reactions. These findings support the concept that bridging of receptors rather than polymerization of IgE molecules is responsible for the activation of membrane-associated enzymes which in turn leads to histamine release.

Animals↗
PubMed1978

On the nature of the presumed receptor for IgE on mast cells. V. Enhanced binding of 125I-labeled IgE to cell-free particulate fractions in the presence of protease inhibitors.

Cell-free particulate preparations derived from sonicated, purified rat peritoneal mast cells can be radiolabeled with IgE. The IgE concentration-dependence and the kinetics of the binding reaction at pH 6.6 were very similar to those observed with intact mast cells. The number of IgE molecules bound per mast cell equivalent at saturation varied somewhat from one particulate preparation to the next and, on average, was about 50% of the binding capacity of the intact cells. Incubation of intact mast cells or of particulate fractions with low concentrations of IgE in serum-free media resulted in a decrease in the amount of bindable IgE which remained in the supernatants in excess over the amount of IgE which was bound to the cells. Specific binding of IgE to both particles and to intact cells at limiting IgE concentrations was stimulated up to approximately twofold by a variety of antibiotic, synthetic or high molecular weight (protein) protease inhibitors of which soybean trypsin inhibitor and p-nitrophenyl-p'-guanidinobenzoate were the most active. These substances also markedly protected the IgE, leaving more of it bindable to rat basophil leukemic cells in a second incubation. Binding to particulate fractions also occurred at pH 4.8 when bovine serum albumin was added to the incubations. The results are consistent with the view that normal peritoneal mast cells have a membrane-bound protease which has high selectivity for IgE.

Binding Sites↗
PubMed1978

Reaginic antibody formation in the mouse. X. Possible role of suppressor T cells in transient IgE antibody responses.

The kinetics of IgE antibody response to alum-absorbed dinitrophenyl derivatives of ovalbumin (DNP-OA) was dependent on the dose of immunogen. A persistent IgE antibody response was obtained when high responder BDF1 mice were immunized with a minimum (0.05 microgram) dose. An increase of the immunogen to 10 microgram depressed IgE antibody responses but enhanced IgG antibody responses of both hapten and carrier specificities. Determination of T helper cell activity and B memory cells after immunization with different doses of antigen indicated that minimum immunogen was favorable for developing helper activity, whereas 1 to 10 microgram immunogen were more favorable than a 0.05-microgram dose for developing both IgE and IgG B memory cells. Nevertheless, neither helper T cells nor B memory cells in the spleen explains a transient IgE antibody response to a high (10 microgram) dose of DNP-OA. Evidence was obtained that immunization with 10 microgram OA induced generation of antigen-specific suppressor T cells, which were not detectable after immunization with 0.05 microgram OA. Transfer of suppressor T cells to DNP-OA-primed mice depressed both anti-hapten and anti-carrier IgE antibody responses. The results suggested strongly that suppressor T cells are involved in a transient IgE antibody response to a high-dose immunogen.

Animals↗
PubMed1978

Development of IgE-forming cells in vitro from rat mesenteric lymph node cells.

Mesenteric lymph node cells from normal rats and rats infected with Nippostrongylus brasiliensis (Nb) were cultured with pokeweed mitogen (PWM) or Nb antigen, and the development of IgM-, IgG2a-, or IgE-containing cells was assessed by immunofluorescence. Normal lymph node cells stimulated with PWM developed into both IgM- and IgE-containing cells, whereas similar stimulation of cells from Nb-infected rats resulted in the development of IgM-, IgG2a-, and IgE-containing cells. The in vitro plasma cell response to PWM was dependent on the presence of T lymphocytes. Lymph node cells from Nb-infected rats responsed to Nb antigen and developed into plasma cells of IgM, IgG, and IgE classes. The response was antigen specific and required antigen-primed T cells. Depletion of IgE-bearing cells or IgM-bearing cells before stimulation with either PWM or Nb antigen diminished the level of IgE forming cell development, suggesting that IgE-IgM double bearing cells are precursors of IgE-forming cells. The distribution of the three isotypes among the If-forming cells that developed in response to PWM was influenced by the source of both B and T cells. When B cells from Nb-infected rats were employed as a source of precursors, T cells from infected animals were more effective than normal T cells for the development of IgE-forming cells, whereas the latter cells were more effective for the development of IgG2a-forming cells than T cells from infected animals.

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