| First Author | Wright SD | Year | 1990 |
| Journal | FASEB J | Volume | 4 |
| Pages | A1848 (Abstr.) | Mgi Jnum | J:12929 |
| Mgi Id | MGI:61145 | Citation | Wright SD (1990) CD14, a leukocyte membrane protein that functions in the response to endotoxin. FASEB J 4:A1848 (Abstr.) |
| abstractText | Full text of Abstract: BIOCHEMISTRY AND PHARMACOLOGY OF ENDOTOXINS I (904-905). CD14, A LEUKOCYTE MEMBRANE PROTEIN THAT FUNCTIONS IN THE RESPONSE TO ENDOTOXIN. Samuel D. Wright. The Rockefeller University, New York, NY 10021. Cells respond to mediators, cytokinea, and hormones by expressing receptor proteins that both bind the mediator and signal the cellular response. Leukocytes respond to physiological doses of endotoxin by a variant of this mechanism. Serum contains binding proteins such as 1ipopolysaccharde binding protein (LBP) which form high affinity complexes with LPS. The LPS-LBP complex then interacts with the leukocyte membrane protein, CD14. Blockade of CD14 with mAbs inhibits the binding of LPS-LBP complexes to macrophages, and purified CD14 binds LPS-LBP complexes. Several observations suggest that serum binding proteins and CD14 are necessary for cells to respond to physiological levels of LPS. 100 pg/ml of LPS (highest concentration reported in septic patients) caused no responses in purified PMN or monocytes, but adding purified binding proteins enabled monocytes to respond with brisk synthesis of TNF and enabled PMN to respond with increased expression and activity of adhesion receptors. Similarly, blockade of CD14 with mAbs completely inhibited TNF synthesis in whole blood incubated with 100 pg/ml LPS. Anti-CD14 also prevented purified PMN from responding to complexes of LPS and binding protein. These results suggest a new molecular paradigm for response to LPS. The capacity to bind LPS resides in a soluble protein (LBP), and the capacity to localize the LPS at the membrane resides in CD14. Signalling may be carried out by CD14 or by additional components. |
