Promotion of arthritis and allergy in mice by aminoglycoglycerophospholipid, a membrane antigen specific to Mycoplasma fermentans.
Mycoplasmas, which lack a cell wall and are the smallest self-replicating bacteria, have been linked to some chronic diseases, such as AIDS, rheumatoid arthritis (RA), and oncogenic transformation of cells. Their membrane components (lipoproteins and glycolipids) have been identified as possible causative factors in such diseases. Glycoglycerophospholipid (GGPL)-III, a unique phosphocholine-containing aminoglycoglycerophospholipid, is a major specific antigen of Mycoplasma fermentans, and has been detected in 38% of RA patients. Unlike those of lipoproteins, which induce inflammation via Toll-like receptor 2 (TLR2), the pathologic effects of GGPL-III are poorly understood. RA and metal allergies are chronic inflammatory diseases in which autoantigens have been implicated. Here, we examined the effects of chemically synthesized GGPL-III in murine arthritis and allergy models. GGPL-III alone exhibited little inflammatory effect, but promoted both collagen-induced arthritis and nickel (Ni) allergy, although less powerfully than Escherichia coli lipopolysaccharide. The augmenting effect of GGPL-III on Ni allergy was present in mice deficient in either T cells or active TLR4, but it was markedly weaker in mice deficient in macrophages, interleukin-1, or the histamine-forming enzyme histidine decarboxylase than in their control strains. These results suggest that GGPL-III may play roles in some types of chronic diseases via the innate immune system.
Department of Molecular Regulation, Graduate School of Dentistry, Tohoku University, Sendai, Japan.
Naoki
N
Sato
Takefumi
T
Oizumi
Masayuki
M
Kinbara
Tadasu
T
Sato
Hiromi
H
Funayama
Seiji
S
Sato
Kazuhiro
K
Matsuda
Haruhiko
H
Takada
Shunji
S
Sugawara
Yasuo
Y
Endo
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001168:Arthritis / Q000139:chemically induced* / Q000276:immunology; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000737:chemistry / Q000276:immunology; D006017:Glycolipids / Q000138:chemical synthesis / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D007375:Interleukin-1 / Q000172:deficiency / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000302:isolation & purification; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D016858:Mycoplasma fermentans / Q000737:chemistry* / Q000276:immunology*; D009532:Nickel / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000276:immunology
C106372:1''-phosphocholine-2''-aminodihydroxypropane-3''-phospho-6'-glucopyranosyl-(1'-3)-1,2-dipalmitoylglycerol; D000485:Allergens; D000942:Antigens, Bacterial; D006017:Glycolipids; D007375:Interleukin-1; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009532:Nickel; D003094:Collagen