Tubular bridges for bronchial epithelial cell migration and communication

• Published in: PloS one Vol. 5; no. 1; p. e8930
• Main Authors: Zani, Brett G, Indolfi, Laura, Edelman, Elazer R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.01.2010; Public Library of Science (PLoS)
• Subjects: Arsenic; Biological activity; Biological products; Bridges; Bridges (Structures); Bronchi - cytology; Cell adhesion & migration; Cell Biology/Cell Signaling; Cell Biology/Cytoskeleton; Cell Communication; Cell growth; Cell interactions; Cell migration; Cell Movement; Cell signaling; Cellular structure; Coalescence; Coalescing; Coculture Techniques; Communication; Cysts; Cytokines; Embryogenesis; Embryonic growth stage; Epithelial cells; Epithelial Cells - cytology; Fibroblasts; Gene expression; Growth factors; Health sciences; Humans; Imaging techniques; In vitro methods and tests; In vivo methods and tests; Inflammation; Inhibition; Intercellular signalling; Islands; Kinases; Leukocyte migration; Morphogenesis; Morphology; Oxidative stress; Oxygen; Pathogens; Pathways; Pharmacology; Physiological aspects; Physiology; Physiology/Respiratory Physiology; Prostaglandin endoperoxide synthase; Reactive oxygen species; Signal Transduction; Tumorigenesis; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008930

Biological processes from embryogenesis to tumorigenesis rely on the coordinated coalescence of cells and synchronized cell-to-cell communication. Intercellular signaling enables cell masses to communicate through endocrine pathways at a distance or by direct contact over shorter dimensions. Cellular bridges, the longest direct connections between cells, facilitate transfer of cellular signals and components over hundreds of microns in vitro and in vivo. Using various cellular imaging techniques on human tissue cultures, we identified two types of tubular, bronchial epithelial (EP) connections, up to a millimeter in length, designated EP bridges. Structurally distinct from other cellular connections, the first type of EP bridge may mediate transport of cellular material between cells, while the second type of EP bridge is functionally distinct from all other cellular connections by mediating migration of epithelial cells between EP masses. Morphological and biochemical interactions with other cell types differentially regulated the nuclear factor-kappaB and cyclooxygenase inflammatory pathways, resulting in increased levels of inflammatory molecules that impeded EP bridge formation. Pharmacologic inhibition of these inflammatory pathways caused increased morphological and mobility changes stimulating the biogenesis of EP bridges, in part through the upregulation of reactive oxygen species pathways. EP bridge formation appears to be a normal response of EP physiology in vitro, which is differentially inhibited by inflammatory cellular pathways depending upon the morphological and biochemical interactions between EP cells and other cell types. These tubular EP conduits may represent an ultra long-range form of direct intercellular communication and a completely new mechanism of tissue-mediated cell migration.