title: Modification of type I collagenous gels by alveolar epithelial cells.
abstract: Contraction of type I collagen gels is an in vitro model of tissue remodeling. In addition to fibroblasts, some epithelial cells can mediate this process. We therefore hypothesized that alveolar epithelial cells might contract extracellular matrices and have the potential to directly participate in the remodeling of the lung after alveolar injury. A549 cells were plated on top of collagen gels, and the gels were floated in culture medium. A549 cells contracted the gels in a time- and cell density-dependent manner. A549 cells, as well as human bronchial epithelial cells (HBEC) and rat alveolar epithelial cells (RalvEC) contracted collagen gels more when they were plated on top of the gel than when they were embedded inside, in contrast to human fetal lung fibroblast (HFL1), which contracted more when cast inside. The amount of hydroxyproline in the collagen gels remained unchanged throughout the contraction. Anti-beta(1) integrin antibody inhibited A549 cell-mediated contraction. Transforming growth factor beta augmented the contraction by A549 cells as well as that by HBEC and HFL1. Prostaglandin E(2) inhibited the contraction by HFL1 but did not affect the contraction by A549 cells, HBEC, or RalvEC. Cytomix (a mixture of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma) inhibited the contraction by HFL1 but strongly enhanced the contraction by A549 cells. Cytomix also caused a morphologic change of A549 cells from a polygonal to a spindle shape. Immunocytochemistry showed that cytomix induced alpha-tubulin expression in A549 cells, whereas cytokeratin, vimentin, smooth muscle actin, beta(1) integrin, and paxillin expressions were not changed. This study thus demonstrates that alveolar epithelial cells can cause contraction of extracellular matrices and that this process is modulated by exogenous mediators, which also modify the microtubular system. Such an activity might contribute to alveolar remodeling after injury.
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5125, USA.
authors.forename: T
authors.initials: T
authors.lastname: Umino
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: L S
authors.initials: LS
authors.lastname: Manouilova
authors.forename: J R
authors.initials: JR
authors.lastname: Spurzem
authors.forename: M
authors.initials: M
authors.lastname: Patricia Leuschen
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology*; D002452:Cell Count / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods; D048429:Cell Size / Q000502:physiology; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000032:analysis; D015232:Dinoprostone / Q000494:pharmacology; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D005333:Fetus / Q000166:cytology; D005455:Fluorescent Antibody Technique; D005782:Gels; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D019012:Integrin beta1 / Q000276:immunology; D051419:Paxillin; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000502:physiology; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014404:Tubulin / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D003598:Cytoskeletal Proteins; D005782:Gels; D019012:Integrin beta1; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; C496063:Pxn protein, rat; D016212:Transforming Growth Factor beta; D014404:Tubulin; D003094:Collagen; D015232:Dinoprostone; D006909:Hydroxyproline