Immunobiological properties of chemically defined lipid A from lipopolysaccharide of Porphyromonas (Bacteroides) gingivalis.
Porphyromonas gingivalis 381 lipid A, characterized by beta-(1-6)-linked glucosamine disaccharide 1-phosphate, with one hydroxyacyl group and one acyloxyacl group, i.e., 3-hydroxy-15-methyl-hexadecanoyl and 3-hexadecanoyloxy-15-methylhexadecanoyl groups at the 2 and 2' positions, respectively, was less endotoxically active than the synthetic Escherichia-coli-type lipid A (compound 506), which possesses beta-(1-6)-linked glucosamine disaccharide 1,4'-bisphosphate, with two acyloxyacyl groups at the 2' and 3' positions and two 3-hydroxytetradecanoyl group at the 2 and 3 positions and the synthetic Salmonella-type lipid A (compound 516), which has three acyloxyacyl groups at the 2,2' and 3' positions and one hydroxyacyl group at the 3 position. P. gingivalis lipid A exhibited no or very low endotoxic activities, i.e., lethal toxicity in galactosamine-loaded mice, preparative ability for local Shwartzman reaction, pyrogenicity and Limulus test as compared with compounds 506 and 516. However, polyclonal B-cell activation of BALB/c mouse splenocytes was as strong as that of compound 506. Furthermore, P. gingivalis lipid A had stronger immunoadjuvant and hemagglutinating activities than compound 506. The absence of ester-linked phosphate at the 4' position and ester-linked fatty acids, and the presence and positions of fatty acids possessing considerable lengths of acyl chains are unique features of P. gingivalis lipid A, and they differentiate this lipid A from enterobacterial and other lipids A. The good balance between endotoxic properties and beneficial immunobiological activities of P. gingivalis lipid A may be attributable to these features.
Ogawa
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Department of Oral Microbiology, Osaka University, Faculty of Dentistry, Suita, Japan.
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000276:immunology; D006384:Hemagglutination / Q000187:drug effects; D008033:Limulus Test; D008050:Lipid A / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000276:immunology / Q000633:toxicity; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011749:Pyrogens / Q000633:toxicity; D011817:Rabbits; D012475:Salmonella / Q000276:immunology; D012790:Shwartzman Phenomenon / Q000276:immunology
D008050:Lipid A; D008070:Lipopolysaccharides; D011749:Pyrogens