TY - JOUR
T1 - High levels of extracellular matrix metalloproteinase inducer are expressed in lymphangioleiomyomatosis
AU - Odajima, Nao
AU - Betsuyaku, Tomoko
AU - Yoshida, Takayuki
AU - Hosokawa, Takeshi
AU - Nishimura, Masaharu
N1 - Funding Information:
Source of funds: This study was supported by scientific research grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (No. 19590877 to T. B.) and from the Ministry of Health, Labour, and Welfare of Japan to the Respiratory Failure Research Group .
PY - 2010/7
Y1 - 2010/7
N2 - Pulmonary lymphangioleiomyomatosis is pathologically characterized by the proliferation of abnormal smooth muscle-like cells (lymphangioleiomyomatosis cells) that synthesize excess matrix metalloproteinases. Extracellular matrix metalloproteinase inducer is minimally expressed in the healthy lung, but is up-regulated in various lung injuries that are apparently associated with matrix metalloproteinases. We therefore immunohistochemically stained extracellular matrix metalloproteinase inducer in lymphangioleiomyomatosis cells and measured extracellular matrix metalloproteinase inducer in bronchoalveolar lavage fluid using an enzyme-linked immunosorbent assay. We also quantified extracellular matrix metalloproteinase inducer messenger RNA expression in the lung using quantitative reverse transcriptase-polymerase chain reaction. Intense staining for extracellular matrix metalloproteinase inducer in lymphangioleiomyomatosis cells indicated high immunoreactivity. Dual immunofluorescence studies revealed diffuse colocalization between extracellular matrix metalloproteinase inducer and α smooth muscle actin, matrix metalloproteinase-2, or matrix metalloproteinase-9. Although levels of extracellular matrix metalloproteinase inducer messenger RNA did not differ in whole lung homogenates from patients with lymphangioleiomyomatosis and healthy controls (1.7 ± 0.1 versus 1.5 ± 0.2 SE, not significant; both n = 4), lymphangioleiomyomatosis nodules retrieved by laser capture microdissection expressed 5.1 (±1.0 SE)-fold higher levels of extracellular matrix metalloproteinase inducer messenger RNA than lung homogenates (P = .0077, n = 4). Levels of extracellular matrix metalloproteinase inducer were significantly elevated in bronchoalveolar lavage fluid from lymphangioleiomyomatosis patients compared with controls (82.7 ± 19.5 versus 38.6 ± 9.0 SE pg/mL, P = .0497; n = 8 and 9, respectively). Increased levels of extracellular matrix metalloproteinase inducer colocalized with increased matrix metalloproteinases in lymphangioleiomyomatosis cells indicate that it potentially functions in pulmonary lymphangioleiomyomatosis.
AB - Pulmonary lymphangioleiomyomatosis is pathologically characterized by the proliferation of abnormal smooth muscle-like cells (lymphangioleiomyomatosis cells) that synthesize excess matrix metalloproteinases. Extracellular matrix metalloproteinase inducer is minimally expressed in the healthy lung, but is up-regulated in various lung injuries that are apparently associated with matrix metalloproteinases. We therefore immunohistochemically stained extracellular matrix metalloproteinase inducer in lymphangioleiomyomatosis cells and measured extracellular matrix metalloproteinase inducer in bronchoalveolar lavage fluid using an enzyme-linked immunosorbent assay. We also quantified extracellular matrix metalloproteinase inducer messenger RNA expression in the lung using quantitative reverse transcriptase-polymerase chain reaction. Intense staining for extracellular matrix metalloproteinase inducer in lymphangioleiomyomatosis cells indicated high immunoreactivity. Dual immunofluorescence studies revealed diffuse colocalization between extracellular matrix metalloproteinase inducer and α smooth muscle actin, matrix metalloproteinase-2, or matrix metalloproteinase-9. Although levels of extracellular matrix metalloproteinase inducer messenger RNA did not differ in whole lung homogenates from patients with lymphangioleiomyomatosis and healthy controls (1.7 ± 0.1 versus 1.5 ± 0.2 SE, not significant; both n = 4), lymphangioleiomyomatosis nodules retrieved by laser capture microdissection expressed 5.1 (±1.0 SE)-fold higher levels of extracellular matrix metalloproteinase inducer messenger RNA than lung homogenates (P = .0077, n = 4). Levels of extracellular matrix metalloproteinase inducer were significantly elevated in bronchoalveolar lavage fluid from lymphangioleiomyomatosis patients compared with controls (82.7 ± 19.5 versus 38.6 ± 9.0 SE pg/mL, P = .0497; n = 8 and 9, respectively). Increased levels of extracellular matrix metalloproteinase inducer colocalized with increased matrix metalloproteinases in lymphangioleiomyomatosis cells indicate that it potentially functions in pulmonary lymphangioleiomyomatosis.
KW - Bronchoalveolar lavage
KW - Immunohistochemistry
KW - Laser capture microdissection
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U2 - 10.1016/j.humpath.2009.12.009
DO - 10.1016/j.humpath.2009.12.009
M3 - Article
C2 - 20236683
AN - SCOPUS:77953287374
SN - 0046-8177
VL - 41
SP - 935
EP - 943
JO - Human Pathology
JF - Human Pathology
IS - 7
ER -