High levels of extracellular matrix metalloproteinase inducer are expressed in lymphangioleiomyomatosis.
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 alpha 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.
First Department of Medicine, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
Nao
N
Odajima
Tomoko
T
Betsuyaku
Takayuki
T
Yoshida
Takeshi
T
Hosokawa
Masaharu
M
Nishimura
D000328:Adult; D051926:Basigin / Q000096:biosynthesis* / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D018192:Lymphangioleiomyomatosis / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis
D012333:RNA, Messenger; D051926:Basigin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9