MONOCYTES CAN PHAGOCYTOSE GRAM-NEGATIVE BACTERIA BY A CD14-DEPENDENT MECHANISM

Phagocytosis of bacteria by monocytes and neutrophil granulocytes prov ides an important first line of defense against bacterial infections, Opsonization of bacteria with complement and phagocytosis by neutrophi ls is dependent on divalent cations and does not take place in blood t hat has been anticoagulated with EDTA. Monocytes, however, do carry ou t phagocytosis even in the presence of EDTA. We show here that this di valent cation-independent phagocytosis pathway requires the presence o f the LPS receptor CD14 on the cell surface, This pathway is dependent on the availability of LPS binding protein, can be blocked by anti-CD 14 Abs, by an excess of soluble CD14, by excess free LPS, or by an exc ess of unlabeled Cram;negative bacteria. In contrast, intact Gram-posi tive bacteria fail to inhibit this process, These experiments define a CD14-dependent phagocytosis pathway for Gram-negative bacteria that o perates in monocytes in human whole blood, This pathway may be able to deal with bacterial pathogens that have developed resistance to compl ement-dependent opsonization and phagocytosis by neutrophils.