Antibody-mediated translocation

The acid-triggered bispecific antibodies mediated the cytotoxicity of CRM107, CRM45, and several genetically engineered DT constructs that are ordinarily inactive because they cannot bind to cells. The kinetics for inhibition of cellular protein synthesis was identical for the bispecific antibody/ CRM 107 complex and native DT, giving a tm = 20 min for the rapid phase (5). This implies both that the acid-induced release of CRM from the antibody carrier is fast and that translocation of its enzymatic domain into the cytosol is facilitated by its transmembrane domain in the same way as native DT. 

A EXPERIMENTAL FIGURE 11-43 Fusion proteins from expression vectors demonstrate that the hormone-binding domain of the glucocorticoid receptor (GR) mediates translocation to the nucleus in the presence of hormone. Cultured animal cells were transfected with expression vectors encoding the proteins diagrammed at the bottom. Immunofluorescence with a labeled antibody specific for p-galactosidase was used to detect the expressed proteins in transfected cells, (a) In cells that expressed p-galactosidase alone, the enzyme... 

Figure 1. Schematic representations of significant biological functions displayed by host-guest complexation in homogeneous solutions or at membrane surfaces, (a) Separation (e.g., antibody-antigen complex formation), (b) Transformation (e.g., enzymatic reaction), (c) Translocation (e.g., carrier- or channel-mediated transport), (d) Transduction (e.g., receptor-mediated transmembrane signaling).

Inhibition of the normal immune response results from a gradual destruction of lymphoid tissue, followed by a decline in antibody production and a decrease in the numbers of eosinophils, basophils, and lymphocytes. The reduction in T-lymphocyte counts by glucocorticoids can occur acutely as a result of the redistribution of these cells from the intravascular space to the spleen, lymph nodes, and bone marrow. Thus an increase in the neutrophil count is commonly observed after glucocorticoid administration. The major suppressive effects of glucocorticoids on the inflamniatory response and the immune system appear to be through the modulation of cytokine production via an inhibition of nuclear factor kappa B (NF-kB) expression and nuclear translocation. Cytoldnes released from immunocompetent cells mediate both the acute and chronic phases of inflammation and participate in the control of the immune response (see Chapter 22). 

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