Immunobiological properties of chemically defined lipid A from lipopolysaccharide of Porphyromonas (Bacteroides) gingivalis.

Abstract

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.