PHYSICOCHEMICAL CHANGES IN ENDOTOXIN ASSOCIATED WITH LOSS OF BIOLOGICAL POTENCY

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Abstract
Ribi, Edgar(National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratory, Hamilton, Mont.),Willard T. Haskins, Kelsey C. Milner, Robert L. Anacker, Daniel B. Ritter, Granville Goode, Robert-John Trapani, and Maurice Landy. Physicochemical changes in endotoxin associated with loss of biological potency. J. Bacteriol.84:803–814. 1962.—The preparation of endotoxins whose gross chemical composition approached that of refined polysaccharide haptenes raised anew the question of which features of composition and structure are essential for their characteristic host reactivity. Alterations in the physicochemical, immunochemical, and biological properties ofSalmonella enteritidisendotoxin subjected to hydrolysis with 0.1nacetic acid were therefore investigated to relate physical characteristics to biological attributes. As hydrolysis proceeded, the decline in biological potency was paralleled by dissociation of endotoxin into particles of the size of haptenic polysaccharide. The potency still present at various stages of hydrolysis could be accounted for by residual undissociated endotoxin. These findings are consistent with the hypothesis that a macromolecular complex of critical size is one of the major requirements for endotoxin to elicit its characteristic effects in the mammalian host.