Symposium on bacterial endotoxins. III. Metabolic effects of endotoxins on mammalian cells.

نویسندگان

  • M W WOODS
  • M LANDY
  • J L WHITBY
  • D BURK
چکیده

The endotoxins of gram-negative bacteria in minute amounts elicit an array of characteristic physiological alterations in mammals including such diverse phenomena as production of fever (1, 3), stimulation of resistance to infection (12, 21, 29), and protection against radiation injury (26). Higher dosage induces a state of stress, acute shock, or eventual death. In tumorbearing animals, extensive intratumoral hemorrhage is associated with necrotization of the malignant tissue (25). In the present paper the occurrence of a possible metabolic common denominator in this wide range of phenomena will be considered. Previous work (10, 31, 32) has demonstrated an insulin :anti-insulin hormonal mechanism that regulates the rate of glycolysis in certain tumors and normal tissues. Three years ago, as the result of metabolic studies in vitro in a series of experimental tumors, we observed that endotoxins exerted a stimulatory effect on cell glycolysis remarkably similar to the action of insulin (33). Endotoxin in concentrations of 0.003 to 0.3 Ag per ml stimulated the formation of acid aerobically from glucose as much as severalfold; at the same time, oxygen uptake remained essentially unaffected. Anaerobic glycolysis was stimulated to a lesser extent. In certain tumors, glycolysis and growth are inhibited by a state of stress in the host (10, 31). This glycolytic inhibition, which apparently involves steroid action, is reversed in vitro by insulin. In such tumors, endotoxin was found to exert an effect remarkably similar to that of insulin (33, 34). Since insulin stimulation often masked glycolytic stimulation by endotoxin, a 1 This symposium was held at the Annual Meeting of the American Society for Microbiology in Chicago, Ill., 24 April 1961, under the sponsorship of the Division of Medical Bacteriology and Immunology with Maurice Landy as convener. 2 Present address: Queen Elizabeth Hospital, Birmingham, England. common locus of action was suggested. Moreover, glycolysis in tumors not sensitive to stress, or to insulin, remained unaffected by endotoxin. We were particularly impressed by the fact that the degree of stimulation of tumor glycolysis observed in vitro with a series of endotoxin preparations paralleled their potencies in eliciting endotoxic phenomena in vivo (33). Furthermore, reduction in the host-reactive properties of endotoxin by an enzyme system present in normal serum (13), or in liver homogenate (28), was paralleled by a similar decrease in its effect on glycolysis (33). These, and other findings, led us to postulate that the properties required for elicitation of reactions in the host by such macromolecular materials were the same as those involved in influencing glycolysis in vitro. It appeared likely, as we had previously shown for insulin, that these glycolytic effects of endotoxin resulted from a specific counteraction of the endogenous, stress-modifiable inhibitor mechanism that controls glucose metabolism. The tumors employed in these studies have proved to be unusually favorable tools for studying the metabolic actions of endotoxin and insulin. The phenomena observed, however, are by no means unique for malignant tissues. Cohn and Morse (4-6) reported glycolytic stimulation, without respiratory impairment, with rabbit polymorphonuclear leukocytes. Of great importance was the fact that they correlated this glycolytic stimulation with an enhancement of phagocytic capacity, a phenomenon already shown by Sbarra and Karnovsky (19, 20) and Karnovsky and Sbarra (11) to be dependent on glycolysis. Cohn and Morse (5, 6) pointed out that it was not possible to decide from their experiments whether the endotoxin-induced stimulation of leukocyte glycolysis was an expression of increased membrane permeability or a direct enzymatic interaction. Yunis and Harrington (35) reported that pyrogenic polysaccharides stimulated glycolysis in normal bone

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عنوان ژورنال:
  • Bacteriological reviews

دوره 25  شماره 

صفحات  -

تاریخ انتشار 1961