Gross, Philipp and Brandl, Katharina and Dierkes, Christine and Schoelmerich, Juergen and Salzberger, Bernd and Glueck, Thomas and Falk, Werner (2009) Lipopolysaccharide-Trap-Fc, a Multifunctional Agent To Battle Gram-Negative Bacteria. INFECTION AND IMMUNITY, 77 (7). pp. 2925-2931. ISSN 0019-9567,
Full text not available from this repository. (Request a copy)Abstract
The family of Toll-like receptors (TLRs) plays a pivotal role in host defense against pathogens. However, overstimulation of these receptors may lead to uncontrolled general inflammation and eventually to systemic organ dysfunction or failure. With the intent to control overwhelming inflammation during gram-negative bacterial sepsis, we constructed soluble fusion proteins of the lipopolysaccharide (LPS)-receptor complex to modulate TLR signaling in multiple ways. The extracellular domain of mouse TLR4 and mouse myeloid differentiation factor 2 (MD-2) fusions (LPS-Trap) were linked to human immunoglobulin G Fc domains (LPS-Trap-Fc). In addition to the ability to bind LPS or gram-negative bacteria and to inhibit interleukin-6 secretion of monocytic cells after LPS treatment, LPS-Trap-Fc was able to opsonize fluorescent Escherichia coli particles. This led to enhancement of phagocytosis by monocytic cells which was strictly dependent on the presence of the Fc region. Moreover, only LPS-Trap-Fc- and not LPS-Trap-coated bacteria were sensitized to complement killing. Therefore, LPS-Trap-Fc not only neutralizes LPS but also, after binding to bacteria, enhances phagocytosis and complement-mediated killing and could thus act as a multifunctional agent to fight gram-negative bacteria in vivo.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EXTRACELLULAR TLR4 DOMAIN; SIGNAL-TRANSDUCTION; ESCHERICHIA-COLI; SOLUBLE FORMS; UNITED-STATES; SEVERE SEPSIS; MD-2; TOLL; RECEPTOR; LPS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Sep 2020 04:56 |
| Last Modified: | 14 Sep 2020 04:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28749 |
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