TY  - JOUR
A1  - Kraft, Sabrina
A1  - Klemis, Verena
A1  - Sens, Carla
A1  - Lenhard, Thorsten
A1  - Jacobi, Christian
A1  - Samstag, Yvonne
A1  - Wabnitz, Guido
A1  - Kirschfink, Michael
A1  - Wallich, Reinhard
A1  - Hänsch, Gertrud Maria
A1  - Nakchbandi, Inaam
T1  - Identification and characterization of a unique role for EDB fibronectin in phagocytosis
T2  - Journal of molecular medicine
N2  - 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.
KW  - Innate immunity
KW  - Bacterial infection
KW  - Phagocytosis
KW  - Fibronectin
KW  - EDB
KW  - EIIIB
KW  - αvβ3 integrin
KW  - Circulation
KW  - Plasma fibronectin
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45738
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-457387
SN  - 1432-1440
SN  - 0946-2716
N1  - 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.
VL  - 94
IS  - 5
SP  - 567
EP  - 581
PB  - Springer
CY  - Berlin ; Heidelberg ; New York, NY
ER  -