Function of CD14 as a peptidoglycan receptor: differences and similarities with LPS

Abstract

Peptidoglycan (PGN) is a macrophage activator from Gram-positive bacteria. PGN activates cells of hemopoietic origin through CD14 since: (i) PGN-unresponsive CD14-negative cells become PGNresponsive after transfection with CD14 and expression of membrane CD14; (ii) PGN binds to CD14 with high affinity; and (iii) anti-CD14 mAbs inhibit both binding of PGN to CD14 and activation of CD14-positive cells by PGN. However, there are several differences in the function of CD14 as PGN and LPS receptor: (i) the kinetics of binding are different; (ii) the affinity of binding in the absence of LPS-binding protein (LBP) is higher for PGN than LPS; (iii) LBP does not increase the affinity of binding of PGN to CD14 and does not enhance cell activation by PGN (in contrast to LPS); (iv) the regions of CD14 needed for binding and activation are partially similar and partially different for PGN and LPS; (v) sCD14:PGN complexes, in contrast to sCD14:LPS complexes, do not activate CD14-negative cells; (vi) PGN, in contrast to LPS, does not activate CHO cells expressing mCD14; and (vii) PGN and LPS induce differential activation of MAP kinases, but activate similar transcription factors (NF-κB, ATF1/CREB, and AP-1).