The lipid A moiety of Porphyromonas gingivalis lipopolysaccharide specifically mediates the activation of C3H/HeJ mice.
The lipid A preparation isolated from Porphyromonas gingivalis was found to induce splenocyte mitogenicity and TNF-alpha release from peritoneal macrophages in LPS-unresponsive C3H/HeJ mice to the same extent as in LPS-responsive mice. In order to clarify whether the activation of C3H/HeJ mice was specifically caused by the lipid A and not by contaminating protein, two strategies were employed. The lipid A fraction from P. gingivalis was subjected to either hydrochloric acid or alkaline treatment to eliminate either glycosylated phosphate or O-acylated fatty acids from the lipid A structure, and the biologic activities of the derivatives were compared in both LPS-responsive and unresponsive C3H/HeJ mice. De-1-O-phosphorylated P. gingivalis lipid A showed partial loss, and de-O-acylated lipid A complete loss of splenocyte mitogenic and TNF-alpha-inductive activities from peritoneal macrophages in both LPS-responsive and unresponsive mice. The relative activities of the intact and treated lipid A compounds in splenocyte mitogenicity and TNF-alpha-inductive activity in macrophages were similar to the relative activities of these preparations in Limulus gelation activities. The LPS-specific antagonist, succinylated lipid A precursor, inhibited P. gingivalis lipid A-mediated splenocyte mitogenicity and TNF-alpha induction in macrophages in a similar manner in LPS-responsive and unresponsive mice. These results strongly suggest that the activation of LPS-unresponsive C3H/HeJ mice by P. gingivalis lipid A was specifically mediated by the lipid A portion and not by contaminating protein. The characteristic action of P. gingivalis lipid A on LPS-unresponsive C3H/HeJ mice was thought to reflect the unique chemical properties of this compound.
Tanamoto
K
K
Division of Microbiology, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
Azumi
S
S
Haishima
Y
Y
Kumada
H
H
Umemoto
T
T
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D008033:Limulus Test; D008050:Lipid A / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D016966:Porphyromonas gingivalis / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000596:Amino Acids; D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha