Lipopolysaccharide (LPS)-Specific Monoclonal Antibodies Regulate LPS Uptake and LPS-Induced Tumor Necrosis Factor-α Responses by Human Monocytes

• Published in: The Journal of infectious diseases 1995-09, Vol.172 (3), p.794-804
• Main Authors: Pollack, Matthew, Espinoza, Ana Maria, Guelde, Gretchen, Koles, Nancy L., Wahl, Larry M., Ohl, Christopher A.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - isolation & purification; Antibodies, Monoclonal - pharmacology; Antibody Specificity; Bacteriology; Biological and medical sciences; Biological Transport; Blood; Cells, Cultured; Chromatography, Affinity; Cytometry; Endotoxins; Escherichia coli; Flow Cytometry; Fluorescein-5-isothiocyanate; Fluorescence; Fundamental and applied biological sciences. Psychology; Humans; Immunoglobulin G - isolation & purification; Immunoglobulin G - pharmacology; Immunoglobulin M - isolation & purification; Immunoglobulin M - pharmacology; Kinetics; Lipopolysaccharides; Lipopolysaccharides - immunology; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacology; Major Articles; Mice - immunology; Microbiology; Monoclonal antibodies; Monocytes; Monocytes - drug effects; Monocytes - immunology; Monocytes - physiology; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Receptors; Salmonella; Salmonella minnesota; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/172.3.794

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-inactivated serum (NHS or ΔNHS) or by LPS-binding protein and inhibited by α-LPS or α-CD14 (LPS receptor) MAbs. The inhibition by α-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 α-complement receptor 1. Monocyte tumor necrosis factor-α responses to LPS were augmented by NHS and ΔNHS and inhibited by α-LPS MAbs. Thus, α-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.