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

Abstract

Lipopolysaccharide (LPS)-monocyte/macrophage 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-inactivated serum (NHS or delta NHS) or by LPS-binding protein and inhibited by alpha-LPS or alpha-CD14 (LPS receptor) MAbs. The inhibition of alpha-LPS uptake was offset in the presence of NHS by a simultaneous MAb-mediated increase in LPS uptake that was blocked by alpha-complement receptor 1. Monocyte tumor necrosis factor-alpha responses to LPS were augmented by NHS and delta NHS and inhibited by alpha-LPS MAbs. Thus, alpha-LPS MAbs down-regulate the proinflammatory uptake of LPS by human monocytes via membrane-bound CD14 while promoting complement-mediated opsonic uptake through membrane-associated CR1.