title: In vitro studies of lymphangioleiomyomatosis.
abstract: Lymphangioleiomyomatosis (LAM) is associated with abnormal airway smooth muscle that leads to the characteristic pathology of lung nodule formation and destruction of lung tissue. The current authors have previously identified abnormal behaviour of airway smooth muscle cells from patients with asthma. In this study, cells and tissue sections derived from patients with LAM (n=7), asthma (n=8), and nonasthmatic controls (n=9) were compared. The presence of the antigen human melanosome (HM)B-45 was investigated, along with the proliferation and release of extracellular matrix proteins, release of endogenous prostaglandin E2 (PGE2), vascular endothelial growth factor and connective tissue growth factor, and the expression of integrins. Positive HMB-45 staining was found in all LAM patients and no controls. Proliferation of LAM cells was not different from control cells nor was its inhibition by beta-agonists, corticosteroids, rapamycin or PGE2. However, endogenous PGE2 levels were markedly decreased in LAM cells, and this was associated with decreased expression of the inducible form of cyclooxygenase (COX-2). The increased levels of connective tissue growth factor seen in asthma cells were not observed in LAM. Elastin mRNA in response to transforming growth factor-beta stimulation was markedly lower in LAM cells than either asthma or control cells. In conclusion, lymphangioleiomyomatosis cells exhibit abnormal properties in vitro that may contribute to pathophysiology and symptomatology in patients with lymphangioleiomyomatosis.
authors.affiliation: Dept of Pharmacology, University of Sydney, NSW 2006, and Transplant Unit, St Vincents Hospital, Sydney, Australia. judblack@med.usyd.edu.au
authors.forename: J L
authors.initials: JL
authors.lastname: Black
authors.forename: Q
authors.initials: Q
authors.lastname: Ge
authors.forename: S
authors.initials: S
authors.lastname: Boustany
authors.forename: P R A
authors.initials: PR
authors.lastname: Johnson
authors.forename: M H
authors.initials: MH
authors.lastname: Poniris
authors.forename: A R
authors.initials: AR
authors.lastname: Glanville
authors.forename: B G G
authors.initials: BG
authors.lastname: Oliver
authors.forename: L M
authors.initials: LM
authors.lastname: Moir
authors.forename: J K
authors.initials: JK
authors.lastname: Burgess
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D016023:Integrins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008168:Lung; D018192:Lymphangioleiomyomatosis / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000951:Antigens, Neoplasm; C526317:CCN2 protein, human; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D017874:Immediate-Early Proteins; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D055513:Connective Tissue Growth Factor; D051546:Cyclooxygenase 2; D015232:Dinoprostone