Genetic non-responsiveness of murine fibroblasts to bacterial endotoxin

Abstract

LETHAL infections with Gram-negative bacteria are thought to be due in large part to the toxicity of cell wall lipopolysaccharide (endotoxin). The mechanisms of action of lipopolysaccharide (LPS) have recently been clarified by in vitro studies which have helped explain many of the pathophysiological sequelae of endotoxin exposure1,2. C3H/HeJ mice, which are genetically resistant to many of the effects of endotoxin, have proved a valuable model for the systematic investigation of endotoxin-mediated phenomena3–5. Bacterial endotoxins are able to interact in vitro with a variety of cells and serum factors1,2,6 and it is known that LPS acts on murine B lymphocytes as a polyclonal activator for both mitogenesis and immunoglobulin synthesis7. This function has been found to be deficient in the C3H/HeJ mouse3,4. Also, endotoxins activate macrophages8–10, and this function also seems to be deficient in C3H/HeJ mice5 (Ryan, J. L., Glode, L. M. and Nathan, C. F., unpublished observations). To determine if the C3H/HeJ genetic defect in responsiveness to endotoxin is more general, we have investigated the ability of bacterial endotoxin to stimulate C3H/HeJ embryonic fibroblasts. Fibroblasts were chosen because it has recently been shown that they are endotoxin sensitive cells11.

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RYAN, J., MCADAM, K. Genetic non-responsiveness of murine fibroblasts to bacterial endotoxin. Nature 269, 153–155 (1977). https://doi.org/10.1038/269153a0

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