Lipopolysaccharide (LPS)-specific monoclonal antibodies regulate LPS uptake and LPS-induced tumor necrosis factor-alpha responses by human monocytes

Lipopolysaccharide (LPS)-monocytelmacrophage interactions are central to the infected host's inflammatory response to gram-negative bacteria. Flow cytometry was used to analyze the regulation by LPS-specific monoclonal antibodies (MAbs) of fluorescein isothiocyanate-conjugated LPS uptake by human peripheral blood monocytes. The uptake of LPS was stimulated by fresh or heat-inacti-vated serum (NHS or aNHS) or by LPS-binding protein and inhibited by a-LPS or a-CD14 (LPS receptor) MAbs. The inhibition by a-LPS MAbs of CD14-mediated LPS uptake was offset in the presence of NHS by a simultaneous MAb-mediated increase in LPS uptake that was blocked by a-complement receptor 1. Monocyte tumor necrosis factor-a responses to LPS were augmented by NHS and aNHS and inhibited by a-LPS MAbs. Thus, a-LPS MAbs down-regulate the proinflam-matory uptake of LPS by human monocytes via membrane-bound CD14 while promoting comple-ment-mediated opsonic uptake through membrane-associated CR1. Monocytes and macrophages are central participants in the infected host's inflammatory and immune responses to bacterial lipopolysaccharides (LPS). The recognition of LPS by specific cellular membrane receptors appears to initiate many of thes