CD14 and apoptosis

In addition to its role as a mediator of innate pro-inflammatory responses following bacterial lipopolysaccharide (LPS) binding, the 55kDa glycosyl-ph osphatidylinositol-linked macrophage plasma membrane glycoprotein CD14 is n ow also known to play a role in phagocytic clearance of apoptotic cells. Al though apoptotic cell-associated ligand(s) for CD14 await definition, initi al findings suggest that ligand binding occurs close to, or at the same sit e as, LPS binding. Significantly, in contrast to LPS clearance and in keepi ng with the non-phlogistic nature of apoptosis, CD14-dependent engulfment o f apoptotic cells fails to elicit pro-inflammatory cytokine release from ma crophages. Therefore CD14 may be regarded as an innate immune receptor both for microbial products-after binding which activates inflammatory response s-and for self components, which either fail to induce, or alternatively ac tively suppress, inflammatory responses. Here we review current knowledge o f the structure and functions of CD14, its ligands, its possible modes of s ignal transduction and its place in the panoply of macrophage molecules imp licated in apoptotic-cell clearance.