Identification and characterization of a unique role for EDB fibronectin in phagocytosis

Plasma fibronectin is a circulating protein that facilitates phagocytosis by connecting bacteria to immune cells. A fibronectin isoform, which includes a sequence of 90 AA called extra-domain B (EDB), is synthesized de n
Plasma fibronectin is a circulating protein that facilitates phagocytosis by connecting bacteria to immune cells. A fibronectin isoform, which includes a sequence of 90 AA called extra-domain B (EDB), is synthesized de novo at the messenger RNA (mRNA) level in immune cells, but the reason for its expression remains elusive. We detected an 80-fold increase in EDB-containing fibronectin in the cerebrospinal fluid of patients with bacterial meningitis that was most pronounced in staphylococcal infections. A role for this isoform in phagocytosis was further suggested by enhanced EDB fibronectin release after internalization of Staphylococcus aureus in vitro. Using transgenic mouse models, we established that immune cell production of fibronectin contributes to phagocytosis, more so than circulating plasma fibronectin, and that accentuated release of EDB-containing fibronectin by immune cells improved phagocytosis. In line with this, administration of EDB fibronectin enhanced in vitro phagocytosis to a larger extent than plasma fibronectin. This enhancement was mediated by αvβ3 integrin as shown using inhibitors or cells from β3 integrin knockout mice. Thus, we identified both a novel function for EDB fibronectin in augmenting phagocytosis over circulating plasma fibronectin, as well as the mediating receptor. Our data also establish for the first time, a direct role for β3 integrin in bacterial phagocytosis in mammals.
show moreshow less

Metadaten
Author:Sabrina Kraft, Verena Klemis, Carla Sens, Thorsten Lenhard, Christian Jacobi, Yvonne Samstag, Guido Wabnitz, Michael Kirschfink, Reinhard Wallich, Gertrud Maria Hänsch, Inaam Nakchbandi
URN:urn:nbn:de:hebis:30:3-457387
DOI:http://dx.doi.org/10.1007/s00109-015-1373-0
ISSN:1432-1440
ISSN:0946-2716
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=26637426
Parent Title (English):Journal of molecular medicine
Publisher:Springer
Place of publication:Berlin ; Heidelberg ; New York, NY
Document Type:Article
Language:English
Year of Completion:2015
Date of first Publication:2015/12/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/02/22
Tag:Bacterial infection; Circulation; EDB; EIIIB; Fibronectin; Innate immunity; Phagocytosis; Plasma fibronectin; αvβ3 integrin
Volume:94
Issue:5
Pagenumber:15
First Page:567
Last Page:581
Note:
Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
HeBIS PPN:432001026
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

$Rev: 11761 $