Biological Properties of Lipid A Isolated fromFlavobacterium meningosepticum

Abstract
The biological properties of the lipid A fromFlavobacterium meningosepticum, which we recently isolated and whose complete chemical structure has been determined (H. Kato, T. Iida, Y. Haishima, A. Tanaka, and K. Tanamoto. J. Bacteriol. 180:3891–3899, 1998), were studied. The lipid A exhibited generally moderate activity compared toSalmonella entericasubsp.entericaserovar abortus equi lipopolysaccharide (LPS) used as a control in the assay systems tested; lethal toxicity in galactosamine-sensitized mice, mitogenicity in mouse spleen cells, induction of tumor necrosis factor alpha (TNF-α) release from mouse peritoneal macrophages and J774-1 mouse macrophage-like and human THP-1 line cells, nitric oxide induction activity from J774-1 cells, andLimulusgelation activity. The moderate activity of theF. meningosepticumlipid A may be explained by its unique fatty acid composition and the lack of a phosphate group in position 4′. It is noteworthy that the lipid A apparently induced TNF-α release from peritoneal macrophages in LPS-unresponsive C3H/HeJ mice and that the activation was suppressed by the LPS-specific antagonist, succinylated lipid A precursor. Significant splenocyte mitogenicity in C3H/HeJ mice was also observed with the lipid A. Taken together with the previous results concerningPorphyromonas gingivalislipid A, which has a high level of structural similarity to the lipid A ofF. meningosepticum, and the induction of TNF-α release in macrophages from C3H/HeJ mice, the lipid A ofF. meningosepticum, which has novel fatty acids, may possibly play an role for the activation of C3H/HeJ macrophages.