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 en dotoxin receptor) and binds to both soluble and membrane CD14, Since s oluble CD14-lipopolysaccharide (LPS) complexes activate CD14-negative endothelial and epithelial cells, this study tested whether soluble CD 14-PGN complexes activate human umbilical vein endothelial cells and e pithelial-like U373 cells to secrete interleukin (IL)-6, express vascu lar cellular adhesion molecule-1, and translocate nuclear factor-kappa B. In contrast to LPS, endothelial, epithelial, and other cells of no n-hemopoietic origin were unresponsive to PGN through soluble or membr ane-bound CD14, whereas cells of hemopoietic origin were responsive to both PGN and LPS. PGN, similarly to LPS, activated endothelial and ep ithelial cells indirectly in the presence of 2%-4% blood, by inducing secretion of both tumor necrosis factor-alpha and IL-I from monocytes. These results reveal different mechanisms of CD14 function and cell a ctivation for LPS and PGN and also demonstrate strong indirect activat ion of endothelial and epithelial cells by both PGN and LPS.