Abstract
An analysis of which component of lipopolysaccharide, the lipid or the polysaccharide, is mitogenic for mouse B-lymphocytes has been performed. A purified glycolipid derived from a rough mutant of Salmonella minnesota (R595) that does not contain any o-polysaccharide at all is more mitogenic than an intact lipopolysaccharide derived from a smooth strain of S. minnesota. Results using fractions produced by several different chemical modifications of whole lipopolysaccharide confirm this result. Acid hydrolysis separates lipopolysaccharide into two components. The lipid fraction is mitogenic, whereas the polysaccharide fraction is not. Those procedures which degrade or modify only the lipid moiety while preserving the antigenic integrity of the polysaccharide also destroy mitogenicity. These include alkaline hydrolysis and deacylation by a more specific treatment with potassium methylate. The lipid preparations are fully active on highly purified B-lymphocyte populations (prepared by anti-theta antiserum and complement), whereas they have no effect on highly purified T-lymphocyte populations (prepared by anti-immunoglobulin and complement). These data demonstrate that the lipid moiety of endotoxin is the B-lymphocyte mitogen, whereas the polysaccharide has no demonstrable mitogenic activity.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andersson J., Melchers F., Galanos C., Lüderitz O. The mitogenic effect of lipopolysaccharide on bone marrow-derived mouse lymphocytes. Lipid A as the mitogenic part of the molecule. J Exp Med. 1973 Apr 1;137(4):943–953. doi: 10.1084/jem.137.4.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Andersson J., Möller G., Sjöberg O. Selective induction of DNA synthesis in T and B lymphocytes. Cell Immunol. 1972 Aug;4(4):381–393. doi: 10.1016/0008-8749(72)90040-8. [DOI] [PubMed] [Google Scholar]
- Bianco C., Nussenzweig V. Theta-bearing and complement-receptor lymphocytes are distinct populations of cells. Science. 1971 Jul 9;173(3992):154–156. doi: 10.1126/science.173.3992.154. [DOI] [PubMed] [Google Scholar]
- Gery I., Krüger J., Spiesel S. Z. Stimulation of B-lymphocytes by endotoxin. Reactions of thymus-deprived mice and karyotypic analysis of dividing cells in mice bearing T 6 T 6 thymus grafts. J Immunol. 1972 Apr;108(4):1088–1091. [PubMed] [Google Scholar]
- Gewurz H., Mergenhagen S. E., Nowotny A., Phillips J. K. Interactions of the complement system with native and chemically modified endotoxins. J Bacteriol. 1968 Feb;95(2):397–405. doi: 10.1128/jb.95.2.397-405.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gmeiner J., Lüderitz O., Westphal O. Biochemical studies on lipopolysaccharides of Salmonella R mutants. 6. Investigations on the structure of the lipid A component. Eur J Biochem. 1969 Jan;7(3):370–379. doi: 10.1111/j.1432-1033.1969.tb19618.x. [DOI] [PubMed] [Google Scholar]
- Kasai N., Nowotny A. Endotoxic glycolipid from a heptoseless mutant of Salmonella minnesota. J Bacteriol. 1967 Dec;94(6):1824–1836. doi: 10.1128/jb.94.6.1824-1836.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim Y. B., Watson D. W. Biologically active endotoxins from Salmonella mutants deficient in O- and R-polysaccharides and heptose. J Bacteriol. 1967 Nov;94(5):1320–1326. doi: 10.1128/jb.94.5.1320-1326.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lüderitz O., Galanos C., Risse H. J., Ruschmann E., Schlecht S., Schmidt G., Schulte-Holthausen H., Wheat R., Westphal O., Schlosshardt J. Structural relationship of Salmonella O and R antigens. Ann N Y Acad Sci. 1966 Jun 30;133(2):349–374. doi: 10.1111/j.1749-6632.1966.tb52376.x. [DOI] [PubMed] [Google Scholar]
- Mergenhagen S. E., Gewurz H., Bladen H. A., Nowotny A., Kasai N., Lüderitz O. Interactions of the complement system with endotoxins from a Salmonella minnesota mutant deficient in O-polysaccharide and heptose. J Immunol. 1968 Jan;100(1):227–229. [PubMed] [Google Scholar]
- NOWOTNY A. Endotoxoid preparations. Nature. 1963 Feb 16;197:721–722. doi: 10.1038/197721b0. [DOI] [PubMed] [Google Scholar]
- NOWOTNY A. Relation of structure to function in bacterial O antigens. II. Fractionation of lipids present in Boivin-type endotoxin of Serratia marcescens. J Bacteriol. 1963 Feb;85:427–435. doi: 10.1128/jb.85.2.427-435.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nowotny A., Cundy K. R., Neale N. L., Nowotny A. M., Radvany R., Thomas S. P., Tripodi D. J. Relation of structure to function in bacterial O-antigens. IV. Fractionation of the components. Ann N Y Acad Sci. 1966 Jun 30;133(2):586–603. doi: 10.1111/j.1749-6632.1966.tb52391.x. [DOI] [PubMed] [Google Scholar]
- Peavy D. L., Adler W. H., Smith R. T. The mitogenic effects of endotoxin and staphylococcal enterotoxin B on mouse spleen cells and human peripheral lymphocytes. J Immunol. 1970 Dec;105(6):1453–1458. [PubMed] [Google Scholar]
- Robbins J. H., Gart J. J., Levis W. R., Burk P. G. The millipore filter assay technique for measuring tritiated thymidine incorporation into DNA in leucocyte cultures. Clin Exp Immunol. 1972 Aug;11(4):629–640. [PMC free article] [PubMed] [Google Scholar]
- Tripodi D., Nowotny A. Relation of structure to function in bacterial O-antigens. V. Nature of active sites in endotoxic lipopolysaccharides of Serratia marcescens. Ann N Y Acad Sci. 1966 Jun 30;133(2):604–621. doi: 10.1111/j.1749-6632.1966.tb52392.x. [DOI] [PubMed] [Google Scholar]
- WESTPHAL O., NOWOTNY A., LUDERITZ O., HURNI H., EICHENBERGER E., SCHONHOLZER G. Die Bedeutung der Lipoid-Komponente (Lipoid A) für die biologischen Wirkungen bakterieller Endotoxine (Lipopolysaccharide). Pharm Acta Helv. 1958 Aug-Oct;33(8-10):401–411. [PubMed] [Google Scholar]