Linked Life Data

15056218

Source:http://linkedlifedata.com/resource/pubmed/id/15056218

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-4-1
pubmed:abstractText
Bacterial infections contribfute to the chronicity of connective tissue lesions in part by perturbing extracellular matrix remodelling processes. We examined a novel mechanism by which the major outer sheath protein (Msp) of the spirochaete Treponema denticola disrupts matrix remodelling mediated by intracellular digestion of collagen. The initial collagen-binding step of phagocytosis was examined in human gingival fibroblasts and Rat-2 fibroblasts. Cells were pretreated with Msp or vehicle, and binding of collagen-coated beads was measured by flow cytometry. Exposure to Msp induced a dose- and time-dependent decrease in cells that bound collagen beads; the inhibition of binding was reversed by absorption with anti-Msp antibodies. Msp-treated fibroblasts remained viable but underwent actin reorganization, including the assembly of a dense meshwork of subcortical actin filaments. Shear force assays showed that Msp abrogated collagen-binding interactions in the minimal affinity range required for stable adhesion. Fluorescence microscopy and immunoblotting showed equivalent amounts of beta1 integrin associated with collagen beads bound to Msp- and vehicle-treated cells. Photobleaching experiments found a similar percentage mobile fraction of beta1 integrins recovered in bleached areas of the plasma membrane. In contrast, Msp-induced inhibition of collagen binding was reversed by beta1 integrin affinity-activating antibodies and by latrunculin B, which prevented subcortical actin assembly. We conclude that native Msp of T. denticola inhibits the binding step of collagen phagocytosis in fibroblasts by inducing subcortical actin filament assembly and restricting affinity modulation of beta1 integrins. We suggest that, like Msp, bacterial toxins that target the cytoskeleton may also perturb the signalling networks required for cellular engagement of matrix ligands.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1462-5814
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
485-98
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15056218-Actins, pubmed-meshheading:15056218-Animals, pubmed-meshheading:15056218-Antigens, CD29, pubmed-meshheading:15056218-Antigens, Surface, pubmed-meshheading:15056218-Bacterial Proteins, pubmed-meshheading:15056218-Bicyclo Compounds, Heterocyclic, pubmed-meshheading:15056218-Cell Adhesion, pubmed-meshheading:15056218-Cell Line, pubmed-meshheading:15056218-Collagen, pubmed-meshheading:15056218-Fibroblasts, pubmed-meshheading:15056218-Gingiva, pubmed-meshheading:15056218-Humans, pubmed-meshheading:15056218-Phagocytosis, pubmed-meshheading:15056218-Porins, pubmed-meshheading:15056218-Protein Binding, pubmed-meshheading:15056218-Rats, pubmed-meshheading:15056218-Thiazoles, pubmed-meshheading:15056218-Thiazolidines, pubmed-meshheading:15056218-Treponema, pubmed-meshheading:15056218-Treponemal Infections
pubmed:year
2004
pubmed:articleTitle
The major outer sheath protein of Treponema denticola inhibits the binding step of collagen phagocytosis in fibroblasts.
pubmed:affiliation
CIHR Group in Matrix Dynamics, University of Toronto, 124 Edward Street, Room 450, Toronto, Ontario, Canada M5G 1G6.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't