Aqueous fraction of Sauropus androgynus might be responsible for bronchiolitis obliterans.
OBJECTIVE
Bronchiolitis obliterans (BO) has been reported to develop following ingestion of Sauropus androgynus (SA), a leafy shrub distributed in Southeast Asia. Little is known about direct effects of SA on airway resident cells or haematopoietic cells in vitro. Identification of the SA component responsible for the development of BO would be an important key to elucidate its mechanism. We sought to elucidate the direct effects of SA on airway resident cells or haematopoietic cells and identify the SA element responsible for the pathogenesis of BO.


METHODS
SA dry powder was partitioned into fractions by solvent extraction. Human and murine monocytic cells, epithelial cells and endothelial cells were cultured with SA solution or fractions eluted from SA. We also investigated the effect of SA in vivo using a murine BO syndrome (BOS) model.


RESULTS
The aqueous fraction of SA induced significant increases of inflammatory cytokine and chemokine production from monocytic lineage cells. This fraction also induced significant apoptosis of endothelial cells and enhanced intraluminal obstructive fibrosis in allogeneic trachea allograft in the murine BOS model. We found individual differences in tumour necrosis factor α (TNF-α) production from monocytes of healthy controls stimulated by this aqueous fraction of SA, whereas it induced high-level TNF-α production from monocytes of patients with SA-induced BO.


CONCLUSIONS
These results suggest that an aqueous fraction of SA may be responsible for the pathogenesis of BO.
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine Faculties of Pharmacy, Meijo University, Nagoya, Japan.
Izumi
I
Hashimoto
Kazuyoshi
K
Imaizumi
Naozumi
N
Hashimoto
Hiroshi
H
Furukawa
Yukihiro
Y
Noda
Tsutomu
T
Kawabe
Toyohiro
T
Honda
Tomomi
T
Ogawa
Masaki
M
Matsuo
Naoyuki
N
Imai
Satoru
S
Ito
Mitsuo
M
Sato
Masashi
M
Kondo
Kaoru
K
Shimokata
Yoshinori
Y
Hasegawa
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001989:Bronchiolitis Obliterans / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D029581:Malpighiaceae; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000009:adverse effects* / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha