| First Author | Huber M | Year | 2006 |
| Journal | Eur J Immunol | Volume | 36 |
| Issue | 3 | Pages | 701-11 |
| PubMed ID | 16506285 | Mgi Jnum | J:114827 |
| Mgi Id | MGI:3690205 | Doi | 10.1002/eji.200535593 |
| Citation | Huber M, et al. (2006) R-form LPS, the master key to the activation ofTLR4/MD-2-positive cells. Eur J Immunol 36(3):701-11 |
| abstractText | Lipopolysaccharide (endotoxin, LPS) is a major recognition marker for the detection of gram-negative bacteria by the host and a powerful initiator of the inflammatory response to infection. Using S- and R-form LPS from wild-type and R-mutants of Salmonella and E. coli, we show that R-form LPS readily activates mouse cells expressing the signaling receptor Toll-like receptor 4/myeloid differentiation protein 2 (TLR4/MD-2), while the S-form requires further the help of the LPS-binding proteins CD14 and LBP, which limits its activating capacity. Therefore, the R-form LPS under physiological conditions recruits a larger spectrum of cells in endotoxic reactions than S-form LPS. We also show that soluble CD14 at high concentrations enables CD14-negative cells to respond to S-form LPS. The presented in vitro data are corroborated by an in vivo study measuring TNF-alpha levels in response to injection of R- and S-form LPS in mice. Since the R-form LPS constitutes ubiquitously part of the total LPS present in all wild-type bacteria its contribution to the innate immune response and pathophysiology of infection is much higher than anticipated during the last half century. |
