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 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.
Pollack
M
M
F. Edward Hébert School of Medicine, Dept. of Medicine, USUHS, Bethesda, MD 20814-4799, USA.
Espinoza
A M
AM
Guelde
G
G
Koles
N L
NL
Wahl
L M
LM
Ohl
C A
CA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000494:pharmacology*; D000918:Antibody Specificity; D001692:Biological Transport; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004926:Escherichia coli; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification / Q000494:pharmacology; D007075:Immunoglobulin M / Q000302:isolation & purification / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D012475:Salmonella; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016650:Fluorescein-5-isothiocyanate