LIPOPOLYSACCHARIDE (LPS)-SPECIFIC MONOCLONAL-ANTIBODIES REGULATE LPS UPTAKE AND LPS-INDUCED TUMOR-NECROSIS-FACTOR-ALPHA RESPONSES BY HUMAN MONOCYTES

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 mo noclonal antibodies (MAbs) of fluorescein isothiocyanate-conjugated LP S uptake by human peripheral blood monocytes. The uptake of LPS was st imulated by fresh or heat-inactivated serum (NHS or Delta NHS) or by L PS-binding protein and inhibited by alpha-LPS or alpha-CD14 (LPS recep tor) MAbs. The inhibition by alpha-LPS MAbs of CD14-mediated LPS uptak e was offset in the presence of NHS by a simultaneous MAb-mediated inc rease in LPS uptake that was blocked by alpha-complement receptor 1. M onocyte tumor necrosis factor-alpha responses to LPS were augmented by NHS and Delta NHS and inhibited by alpha-LPS MAbs. Thus, alpha-LPS MA bs down-regulate the proinflammatory uptake of LPS by human monocytes, ia membrane-bound CD14 while promoting complement-mediated opsonic upt ake through membrane-associated CR1.