Effect Of Blocking Antibody Research Articles

Interaction between proximal tubular epithelial cells and infiltrating monocytes/T cells in the proteinuric state

We hypothesize an interaction between T cells/monocytes and the tubules in the development of tubulointerstitial injury in chronic proteinuric nephropathy. We established in vitro co-culture systems of proximal tubular epithelial cells (PTEC) and T cells/monocytes to study the contribution of soluble factors and cell-to-cell contact in the development of tubulointerstitial injury. The release of monocyte chemoattractant protein-1 (MCP1 or CCL2), Regulated upon Activation, normal T cell Expressed and Secreted (RANTES or CCL5), soluble intracellular adhesion molecules-1 (sICAM-1), or interleukin-6 (IL-6) was increased in PTEC following apical exposure to human serum albumin (HSA). The release of CCL2, CCL5, or sICAM-1 from PTEC was enhanced by contact of monocytes/T cells on the basolateral surface. Tumor necrosis factor-alpha (TNF-alpha) and IL-1beta are important soluble factors as suggested by the blocking effect of antibodies (Abs) against TNF-alpha or IL-1beta but not against other cytokines. The percentage of CD4+ T cells expressing both chemokine receptors, CCR2 and CCR5, was increased after culturing with supernatant from the apical or basolateral surface of PTEC following apical exposure to HSA. However, only CCR2 was upregulated in CD8+ T cells, whereas CCR5 expression was increased in monocytes. The chemotaxis of CD4+ or CD8+ T cells to supernatant from PTEC upon apical exposure to HSA was reduced with neutralizing Abs against CCL5 and/or CCL2, whereas the chemotaxis of monocytes was only reduced by anti-CCL5 but not by anti-CCL2. In summary, chemokines released by HSA-activated PTEC are amplified by monocytes/T cells. Mediators released by HSA-activated PTEC can differentially modulate the expression of chemokine receptors in monocytes/T cells and hence, alter their chemotaxis towards activated PTEC. These interactions are pivotal in the development of tubulointerstitial injury.

Single fibre electromyography in multifocal motor neuropathy with persistent conduction blocks

OBJECTIVETo study the process of denervation-reinnervation in multifocal motor neuropathy with persistent conduction blocks in clinically affected and unaffected muscles.METHODVolitional single fibre electromyography (SFEMG) was performed in the extensor digitorum...

Involvement of a Membrane-bound Form of Glutamate Dehydrogenase in the Association of Lysosomes to Microtubules

A 50-kDa membrane protein corresponding to a membrane-bound isoform of glutamate dehydrogenase was proposed as a molecular species that could mediate lysosome-microtubule interactions. This protein, isolated from purified lysosome membranes, is a peripheral membrane protein with an ATP-dependent microtubule binding activity. We have produced antibodies against the purified 50-kDa protein to investigate its role in the association of lysosomes to microtubules using a cell-free reconstitution assay and cell microinjection. Pretreatment of purified lysosomes with the antibodies inhibited the association of these vesicles to microtubules. The blocking effect of antibodies was demonstrated by a differential sedimentation method and negative staining electron microscopy, allowing us to quantify the amount of microtubules interacting with lysosomes and the proportion of lysosomes bound to microtubules, respectively. Affinity-purified antibodies microinjected into intact cells altered the distribution of lysosomes that appeared less clustered in the vicinity of nuclei. The antibody-induced lysosome dispersion was assessed by quantitative videomicroscope analyses. These data show that the 50-kDa membrane protein could act, through its microtubule binding activity, as a molecule of attachment of lysosomes to microtubules. This membrane-bound isoform of glutamate dehydrogenase could be involved in the microtubule-dependent perinuclear localization of lysosomes.

The blocking effect of antibodies against the products of the H-2 gene complex on lymphocyte complement (C3d) receptors. complement dependence and specificity.

Antisera against the products of the major histocompatibility system (MHS), produced by immunization between congenic mouse strains differing only at that segment of the 17th chromosome rosettes which bears the H-2gene complex, exert a reproducible blocking effect on formation of with EACm (C3d rosettes). In many instances this effect is probably due to specific antibodies reactive with the lymphocytes, as indicated by immunochemical and adsorption experiments. Purified antibodies from the C3H anti-C3H.B10 immune ascites failed to exert this blocking effect. The blocking capacity can be restored, however, by addition of fresh normal mouse, rabbit or fetal calf serum, but not by heat inactivated serum. These experiments show that the presently defined H-2K, H-2D and H-2L antigens as well as some Ia antigens are themselves not the C3d receptors. The blocking effects observed in the presence of complement are possibly due to the proximity of H-2 or Ia molecules and C3d receptors, or to a rearrangement of membrane components after reaction with anti-MHC anti-MHC antibodies and complement.