Bacterial endotoxins (ET) are widely distributed among gram negative bacteria and are considered an important component of their cell walls. There have been extensive chemical, physiological, pharmacologic and immunologic studies concerning ET and its derivatives over the last few decades and excellent reviews summarized these findings. Much evidence exists that the Lipid A portion of ET accounts for the toxic activities of the intact molecule,while the polysaccharide component contains the antigenic moiety of the structure. Many beneficial effects can also be attributed to these important molecules. Studies in this laboratory have shown that detoxified ET as well as hydrolytic split products, free of Lipid A and rich n polysaccharide (PS), have some of the beneficial properties of the parent ET without toxicity. The exact identification of the minimal structural requirements for the elicitation of the various biological effects of the ET was greatly impeded by the lack of chemically pure ET or its split products. ET is heterogenous and the lipid A preparations recently made commercially available are highly contaminated with side products. The endotoxic activity of the same preparation was only about 5-8% of our standard Serratia ET sample. Quite obviously the unfractionated PS preparation also consists of multiple hydrolytic breakdown products of ET. It is evident that such preparations are not suitable for accurate identification of the structural subunits which can elicit the highly desirable beneficial effects of ET. Accordingly, the major goals of this proposed project are to isolate chemically pure ET and PS preparations,fragment them with appropriate procedures and identify the smallest structural subunit which has immunopotentiating and/or immuno-suppressive activity. The molecular and cellular factors involved in the mechanisms of such immunomodulation (IM) induced by these breakdown products will then be analyzed.
| Kovats, E; Somlyo, B; Csanky, E et al. (1992) Potentiation of HIV envelope glycoprotein and other immunogens by endotoxin (ET) and its molecular fragments. Int J Immunopharmacol 14:573-81 |
