Endotoxic properties of free lipid A from Porphyromonas gingivalis.
The relationship between chemical structure and biological activity of the lipid A from Porphyromonas gingivalis, which we recently isolated and whose complete chemical structure was determined [Kumada et al. (1995). J Bacteriol 177, 2098-2106], was studied. The lipid A exhibited endotoxic activity in all the assay systems tested: Limulus gelation activity, lethal toxicity in galactosamine-sensitized mice, mitogenicity in mouse spleen cells and induction of nitric oxide (NO) and tumour necrosis factor alpha (TNF) release from both mouse peritoneal macrophages and the J774-1 mouse macrophage-like cell line. The activity was, however, about 100-fold less than that of Salmonella minnesota LPS used as a control. The moderate activity of the lipid A may be partially explained by its unique fatty acid composition and the lack of a phosphate group in position 4. In contrast, the lipid A as well as whole LPS of P. gingivalis unexpectedly exhibited an even stronger induction of TNF from the human monocytic THP-1 cell line than control LPS when measured by the minimum stimulatory dose. The difference in sensitivity of human and mouse cells to P. gingivalis lipid A suggests that the recognition mechanism, including that for the receptor for endotoxin, may be regulated in different ways in the two cells.
Tanamoto
Ken-Ichi
KI
Division of Microbiology, National Institute of Health Sciences, Setagayaku, Tokyo 158, Japan.
Azumi
Satoko
S
Division of Microbiology, National Institute of Health Sciences, Setagayaku, Tokyo 158, Japan.
Haishima
Yuji
Y
Division of Microbiology, National Institute of Health Sciences, Setagayaku, Tokyo 158, Japan.
Kumada
Hidefumi
H
Department of Oral Microbiology, Kanagawa Dental College, Yokosuka, Kanagawa 238, Japan.|Division of Microbiology, National Institute of Health Sciences, Setagayaku, Tokyo 158, Japan.
Umemoto
Toshio
T
Department of Oral Microbiology, Kanagawa Dental College, Yokosuka, Kanagawa 238, Japan.
D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D006801:Humans; D008033:Limulus Test; D008050:Lipid A / Q000737:chemistry / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008934:Mitogens / Q000737:chemistry / Q000633:toxicity; D009000:Monocytes / Q000187:drug effects; D009569:Nitric Oxide / Q000032:analysis; D016966:Porphyromonas gingivalis / Q000737:chemistry*; D012475:Salmonella / Q000737:chemistry; D013045:Species Specificity; D018675:Toxicity Tests; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001427:Bacterial Toxins; D004731:Endotoxins; D008050:Lipid A; D008070:Lipopolysaccharides; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide