Endothelial and epithelial cells do not respond to complexes of peptidoglycan with soluble CD14 but are activated indirectly by peptidoglycan-induced tumor necrosis factor-alpha and interleukin-1 from monocytes.

Peptidoglycan (PGN) activates macrophages through membrane CD14 (an endotoxin receptor) and binds to both soluble and membrane CD14. Since soluble CD14-lipopolysaccharide (LPS) complexes activate CD14-negative endothelial and epithelial cells, this study tested whether soluble CD14-PGN complexes activate human umbilical vein endothelial cells and epithelial-like U373 cells to secrete interleukin (IL)-6, express vascular cellular adhesion molecule-1, and translocate nuclear factor-kappaB. In contrast to LPS, endothelial, epithelial, and other cells of non-hemopoietic origin were unresponsive to PGN through soluble or membrane-bound CD14, whereas cells of hemopoietic origin were responsive to both PGN and LPS. PGN, similarly to LPS, activated endothelial and epithelial cells indirectly in the presence of 2%-4% blood, by inducing secretion of both tumor necrosis factor-alpha and IL-1 from monocytes. These results reveal different mechanisms of CD14 function and cell activation for LPS and PGN and also demonstrate strong indirect activation of endothelial and epithelial cells by both PGN and LPS.