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

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Abstract
Porphyromonas gingivalis 381 lipid A, characterized by β‐(1–6)‐linked glucosamine disaccharide 1‐phosphate, with one hydroxyacyl group and one acyloxyacyl 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 β‐(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.

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