PubMed · 2716880
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
J H Lockefeer, J van der Heide. 1989-03-25. [Current developments in hepatology].. https://pubmed.ncbi.nlm.nih.gov/2716880/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
BACKGROUND & AIMS: Intrahepatic bile ducts express a range of lymphocyte adhesion molecules during episodes of inflammation. This may contribute to the susceptibility of biliary epithelium to immunologic damage during liver allograft rejection, graft-versus-host disease, and primary biliary cirrhosis. However, no previous study has shown that these adhesion molecules are functional. The aim of this study was to define the molecular basis of lymphoepithelial interactions within the intrahepatic bile ducts. METHODS: Human intrahepatic biliary epithelial cells (HIBECs) were cultured, and their interaction with resting and activated lymphocytes was studied using a flow-cytometric assay that allowed characterization of the adherent cells and functional investigation of individual adhesive interactions. The capacity of adherent cytotoxic lymphoid cells to damage HIBEC was studied using a standard 51Cr release assay. RESULTS: Allogeneic lymphocytes were bound by HIBECs; this adherence was increased by activation of either participating cell type. Cells with cytotoxic capacity were bound preferentially. At least 50% of the overall adhesion was dependent on lymphocyte function-associated antigen 1. Cytotoxicity assays showed that HIBECs were susceptible to lysis by lymphokine-activated natural killer cells. CONCLUSIONS: This study shows that the adhesion molecules expressed by HIBECs are functional and necessary for the activity of cytotoxic effector lymphocytes.
The adhesive interaction between T lymphocytes and parenchymal cells is of importance for many processes of the cellular immune response. This adhesion is regulated by the activation status of the T cell and by cytokines in the microenvironment which can alter adhesion molecule expression by endothelial and epithelial cells. In this study results from an isotopic adhesion assay were compared with those from a flow cytometric assay in order to determine which was most appropriate for the investigation of lymphocyte adhesion to human umbilical vein endothelial cells (HUVEC) and intrahepatic biliary epithelial cells (HIBEC). Treatment of both these cell types with the proinflammatory cytokines interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) significantly upregulated expression of intercellular adhesion molecule-1 (ICAM-1). Treatment with TNF-alpha also induced endothelial cells to express vascular cell adhesion molecule-1 (VCAM-1). The isotopic assay demonstrated increased adhesion of lymphoblasts to HUVEC which had been stimulated with cytokines for 15 h but failed to detect major changes in adhesion following 72 h of cytokine treatment of HUVEC or HIBEC. However, the flow cytometric assay reproducibly demonstrated increased adhesion following cytokine treatment for both these time periods; these increases corresponded with the changes in adhesion molecule expression by cytokine-stimulated HUVEC and HIBEC targets. The differences in apparent adhesion measured by the two assays after cytokine stimulation for 72 h may be explained by cytokine-induced changes in the morphology and confluency of cultured cells. Results of the isotopic assay are proportional to the total number of lymphoid cells bound by the cultured target cells and will be distorted by changes in effective target cell area. The flow cytometric assay measures the mean number of lymphoid cells bound by each target cell and is independent of the total binding area. It is concluded that the flow cytometric assay is more suitable than the isotopic technique for following time-dependent changes in the adhesion of leukocytes to cytokine-stimulated target cells.
Explore the source record for details and available documents.