| Popis: |
The macrophage is a central participant in the development of septic shock, acute respiratory distress syndrome (ARDS), inflammatory bowel disease, and rheumatoid arthritis. In these, and other inflammatory diseases, macrophages release excessive quantities of pro-inflammatory mediators including nitric oxide (NO), tumor necrosis factor (TNF), interleukin (IL)-l, and IL-6. Exogenous stimulating factors can cause an overexpression of macrophage-derived mediators, as for instance in Gram-negative sepsis caused by bacterial lipopolysaccharide (LPS). In this case, monocytes/macrophages respond to extremely low concentrations of LPS-LPS binding protein (LBP) complexes by interacting with CD 14 on the cell membrane, or by internalizing the LPS-LBP-CD14 complex through endosomal pathways [1]. Although CD 14 is a glycosylphosphatidylinositol (GPI)-anchored membrane protein, it is also a soluble serum protein which can be adopted onto the cell surface to confer LPS sensitivity to unresponsive cells [1, 2, 3]. Membranebound CDI4-LPS-LBP interacts with specific receptors, recently identified as members of the toll-like receptor (TLR) family, that activate intracellular signaling pathways [4]. It appears that one function of CD 14 is to opsonize the LPS-LBP complex, enabling the macrophage to efficiently recognize an invasive threat signaled by the presence of LPS. |
