Experimental pulmonary granuloma mimicking sarcoidosis induced by Propionibacterium acnes in mice.
Propionibacterium acnes has been implicated as an etiologic agent of sarcoidosis since the isolation of this bacterium from sarcoid lesions. We experimentally produced a murine pulmonary granuloma model using P. acnes with several features that simulate sarcoidosis. Mice were sensitized with heat-killed P. acnes and complete Freund's adjuvant and were subsequently challenged with heat-killed P. acnes at 2-week intervals. P. acnes-challenged mice developed epitheloid cell granulomas in the lungs. These mice showed a pulmonary immune response characterized by an increased number of T-lymphocytes, especially CD4+ cells, and the ratio of CD4+/CD8+ in bronchoalveolar lavage (BAL) fluid also increased. Furthermore, significant elevations in both angiotensin-converting enzyme (ACE) serum levels and antibody titers against P. acnes were observed. Mice sensitized with P. acnes without complete Freund's adjuvant were capable of forming pulmonary granulomas, which appeared to be caused by indigenous P. acnes. The genome of P. acnes was found in the lungs, BAL cells, hilar lymph nodes, liver, and spleen in non-sensitized mice, which were thought to be germ-free. These results suggest that the immune response against indigenous P. acnes may play an important role in the pathogenesis of granuloma formation in a murine model.
Iio
Kouji
K
Field of Medical Technology, Graduate School of Health Sciences, Okayama University, Okayama 700-8558, Japan.
Iio
Tomoe Ueno
TU
Okui
Yuhei
Y
Ichikawa
Hirohisa
H
Tanimoto
Yasushi
Y
Miyahara
Nobuaki
N
Kanehiro
Arihiko
A
Tanimoto
Mitsune
M
Nakata
Yasunari
Y
Kataoka
Mikio
M
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004269:DNA, Bacterial / Q000032:analysis; D005260:Female; D006099:Granuloma / Q000209:etiology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011425:Propionibacterium acnes / Q000235:genetics / Q000276:immunology*; D017565:Sarcoidosis, Pulmonary / Q000209:etiology*
D000907:Antibodies, Bacterial; D004269:DNA, Bacterial; D007703:Peptidyl-Dipeptidase A