Tumor necrosis factor alpha binding to bacteria: evidence for a high-affinity receptor and alteration of bacterial virulence properties.

Human and murine receptors for tumor necrosis factor alpha (TNF-alpha) are present on most somatic cells and have been characterized and cloned. In contrast, very little is currently known about whether TNF-alpha can bind to pathogens and whether such binding results in important biological consequences for the infected host. We now report that a number of gram-negative bacteria have receptors for TNF-alpha. Using 125I-labeled TNF-alpha, we show that Shigella flexneri has 276 receptors for TNF-alpha, with a Kd of 2.5 nM. The binding of labeled TNF-alpha to these bacterial receptors can be inhibited by cold TNF-alpha but not by cold TNF-beta. Binding of 125I-TNF-alpha to S. flexneri was inhibited by trypsin treatment of bacterial cells or incubation at 52 degrees C for 3 min. Monoclonal antibody to either the 55-kDa or the 75-kDa TNF-alpha receptor, which are present on different eukaryotic cells, had no effect on 125I-TNF-alpha binding to bacteria. A number of gram-negative bacteria were capable of binding 125I-TNF-alpha. Gram-positive bacteria bound significantly less 125I-TNF-alpha than gram-negative bacteria. Pretreatment of S. flexneri with TNF-alpha resulted in enhanced bacterial invasion of HeLa cells and enhanced uptake by human and murine macrophages. Pretreatment of HeLa cells with antibody to the 55-kDa TNF-alpha receptor abrogated enhanced invasion of HeLa cells by TNF-alpha-bacterium complexes. These results suggest that TNF-alpha-bacterium complexes can interact with TNF-alpha receptors present on eukaryotic cells. This report shows that gram-negative bacteria have receptors for TNF-alpha and that a virulence property of a bacterium is altered as a consequence of cytokine binding.

Palestinian labour mobility.

"Following an overview of demographic and migratory trends since the late 1960s, the article examines labour force participation and analyses the distribution of Palestinian workers between the three labour markets in which they participate: the domestic market of the West Bank and Gaza Strip, the Israeli market and the Arab market, consisting chiefly of Jordan and the oil-rich Arab states. Since 1982 there has been a contraction of employment opportunities for Palestinians in the latter two labour markets. Domestic job creation is one of the main tasks confronting the Palestinian administration to be set up under the 1993 Israel/PLO agreement."

Interferon gamma (IFN-gamma) production by gut-associated lymphoid tissue and spleen following oral Salmonella typhimurium challenge.

Although IFN-gamma has been shown to play an important role in protection against a systemic S. typhimurium challenge, the in vivo and in vitro production of this cytokine following S. typhimurium infection of the gastrointestinal tract has not been investigated. In this study, IFN-gamma production by gut-associated lymphoid tissue and spleen was investigated in mice following oral challenge with S. typhimurium. Cells obtained from the Peyer's patches (PP), mesenteric lymph nodes (MLN) and spleen (Sp) of mice orally challenged with S. typhimurium were assessed for levels of IFN-gamma mRNA after varying times following in vivo infection. RNA obtained from the above tissues was subjected to reverse transcription followed by PCR amplification using primers specific for murine IFN-gamma. Elevated levels of IFN-gamma mRNA were first detected in the PP at 6 h post-challenge. Elevated levels of IFN-gamma mRNA were then detected in the MLN at 24 h and in the spleen at 4 days post-challenge. These in vivo results were in agreement with the ability of these lymphoid tissues to produce IFN-gamma upon in vitro stimulation with killed S. typhimurium. Neutralization of endogenously produced IFN-gamma by administration of mAb to IFN-gamma completely abrogated resistance to an oral challenge of S. typhimurium. A significant difference in the percent mortality was observed between the antibody-treated and control groups. Evaluation of bacterial spread in the antibody treated group versus the control group at 4 days following oral challenge revealed higher numbers of bacteria in the spleen and liver of antibody treated mice. These results clearly show that IFN-gamma is rapidly produced by gut-associated lymphoid tissue and spleen following oral S. typhimurium infection, and that endogenous production of IFN-gamma is essential in host resistance to S. typhimurium.