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Soluble MD-2 activity in plasma from patients with severe sepsis and septic shock
| Content Provider | Scilit |
|---|---|
| Author | Pugin, Jérôme Stern-Voeffray, Sabine Daubeuf, Bruno Matthay, Michael A. Elson, Greg Dunn-Siegrist, Irène |
| Copyright Year | 2004 |
| Description | In this paper, we show that plasma from patients with severe sepsis and septic shock but not normal plasma supports lipopolysaccharide (LPS) activation of epithelial cells expressing Toll-like receptor 4 (TLR4). Recombinant soluble myeloid differentiation protein-2 (MD-2) complemented normal plasma and allowed LPS activation of epithelial cells to levels measured with “septic” plasma, whereas soluble MD-2-depleted plasma lost its effects. The same “MD-2 activity” was found in urine from a patient with septic shock and in lung edema fluids from patients with adult respiratory distress syndrome (ARDS). Recombinant soluble MD-2 enabled LPS-dependent activation of epithelial cells bearing TLR4. LPS-binding protein (LBP) and soluble CD14 increased the sensitivity of TLR4-expressing epithelial cells to LPS but were not able to mediate LPS activation of these cells in the absence of soluble MD-2. An anti-MD-2 monoclonal antibody blocked LPS activation of TLR4-expressing cells only in the presence of septic plasma or septic urine. These results suggest that septic plasma containing soluble MD-2 leaking into the extravascular space supports LPS activation of TLR4-expressing epithelial cells. We therefore propose that soluble MD-2 is an important mediator of organ inflammation during sepsis. (Blood. 2004;104:4071-4079) |
| Related Links | http://www.bloodjournal.org/content/bloodjournal/104/13/4071.full.pdf |
| Ending Page | 4079 |
| Page Count | 9 |
| Starting Page | 4071 |
| DOI | 10.1182/blood-2003-04-1290 |
| Journal | Blood |
| Issue Number | 13 |
| Volume Number | 104 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2004-12-15 |
| Access Restriction | Open |
| Subject Keyword | Hematology Research and Experimental Medicine Epithelial Cells Septic Shock Soluble Md Lipopolysaccharide Urine Sepsis and Septic Inflammation Edema Journal: Blood (Vol- 122, Issue- 13) |
| Content Type | Text |
| Resource Type | Article |
