Recent progress has been made in understanding the diverse effects of bacterial endotoxin (LPS) on animal systems. Experiments from our laboratory, as well as those from several other groups, have provided strong evidence supporting the presence of different sites of interaction with LPS in cells of immunological interest. However, the sequence of expression of receptors, and their interrelations, are poorly understood. In this review, we summarize the essentials of these studies, with particular emphasis on experiments from our own laboratory. Our results suggest that the "positive" signals which trigger the activation of B lymphocytes and bone-marrow cells, as well as the "negative" signals which trigger macrophage desensitization and tolerance to LPS, might be delivered by sparsely represented and yet unidentified LPS receptors. The identification of these molecules would clarify the mechanisms involved in the immunostimulatory as well as in the pathophysiological effects of endotoxin, and should have significant impact upon potential therapeutic intervention in endotoxin-mediated disease.
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