Search PubMed⌕ Search

Biomedical subjects

D Burger

Publications and source records attributed to D Burger.

140 records · Page 8Linked to original sources
PubMedDate not supplied

Enhanced HIV replication in monocytic cells following engagement of adhesion molecules and contact with stimulated T cells.

HIV-infected macrophages form a major reservoir of virus within tissue and are present in multiple tissue sites. Control of HIV replication within this cell population is likely to have profound effects on the pathogenesis of HIV infection. Cell-cell interaction between CD4+ T cells and macrophages is a crucial part of antigen presentation and has the potential to continually seed HIV infection of such T cells, maintaining high levels of infected cells within lymph nodes. Interaction of T cells and macrophages is controlled by engagement of cell membrane adhesion molecules which effect discrete intracellular signalling pathways. We have investigated the effects of cross-linkage of specific adhesion molecules and contact with T cells on HIV replication in chronically infected monocytic cell line OM10.1. Cross-linkage of CD18, CD29 or CD45 by immobilized antibodies specifically enhanced HIV replication in OM10.1 cells; cross-linkage of a panel of other cell surface proteins had no effect on HIV replication. Enhancement of HIV replication following cross-linkage of CD18, CD29 or CD45 was dependent upon TNF alpha secretion. Such adhesion molecules are involved in macrophage adhesion to other cells. In further experiments, we demonstrated that contact of OM10.1 cells with stimulated fixed T cells or isolated T-cell membranes potently enhanced HIV replication in a TNF-dependent manner, while in contrast, unstimulated fixed T cells or T-cell membranes had no effect on HIV replication. Cross-linkage of monocyte cell membrane adhesion molecules on contact with stimulated fixed T cells mimics adhesion molecule ligation induced during antigen presentation. Activation of HIV replication in monocytic cells on T cell-macrophage adhesion during antigen presentation would facilitate HIV infection and subsequent deletion of CD4+ T cells in an antigen-specific manner. This phenomenon may play a role in the sequential loss of antigen specific CD4+ T cells seen in HIV-infected patients.

Antigen Presentation↗
PubMedDate not supplied

Interleukin-1, tumor necrosis factor and their specific inhibitors.

It has become evident during the past years that interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha), mainly produced by monocyte-macrophages, are the principal mediators of tissue destruction in many immuno-inflammatory diseases such as rheumatoid arthritis (RA). However, the discovery of a biologically active monokine of approximately 17 kD preceded the isolation of IL-1 and TNF-alpha as well as their cloning by more than 16 years. The two latter cytokines induce in synergy the production of high levels of matrix metalloproteinases (MMP) by fibroblasts, synovial cells and chondrocytes. The biological activity of MMP is controlled by tissue inhibitor of MMP (TIMP) which also depends on the presence of cytokines in the microenvironment. One of the principal stimuli of the production of IL-1 and TNF-alpha is the direct contact between the membranes of activated lymphocytes and monocyte-macrophages. Several glycoproteins expressed on the surface of activated lymphocytes (CD11, CD69) are implicated in this activation process and can be partially blocked by their respective antibodies. These prompt the decrease of cytokines and proteases in the lymphocyte/monocyte interaction. In the past few years, two pathways for inhibiting the activation of macrophages, fibroblasts and synovial cells have been elucidated. One of them is due to the action of anti-inflammatory cytokines such as IL-4 and IL-10 which considerably decrease production of IL-1, TNF-alpha and metalloproteases. In contrast to IL-4, IL-10 is also capable of stimulating the production of TIMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗