Lipopolysaccharide (LPS)-reactive monoclonal antibodies fail to inhibit LPS-induced tumor necrosis factor secretion by mouse-derived macrophages. 1989

J K Chia, and M Pollack, and G Guelde, and N L Koles, and M Miller, and M E Evans
Department of Medicine, Uniformed Services, University of the Health Sciences, F. Edward Hebert School of Medicine, Bethesda, MD 20814.

Murine monoclonal antibodies (MAbs) reactive with epitopes on the O-side chain, core oligosaccharide, or lipid A of Escherichia coli and Salmonella minnesota lipopolysaccharide (LPS) were evaluated for their ability to inhibit LPS-induced tumor necrosis factor (TNF) secretion by mouse-derived RAW 264.7 macrophages. As little as 50 ng of purified LPS or lipid A stimulated macrophages to produce TNF detectable as cytotoxic activity in an L-929 fibroblast assay. None of 13 MAbs (concentration range, 0.1-1,000 micrograms/mL) blocked LPS- or lipid A (0.025-0.1 micrograms/mL)-induced TNF secretion by RAW 264.7 cells. Rabbit antiserum to synthetic lipid A also failed to block lipid A-induced TNF activity. Similar negative results were obtained when intact bacteria or membrane vesicles were used as TNF inducers. In contrast, polymyxin B, but not the less hydrophobic polymyxin B nonapeptide, produced almost complete inhibition of macrophage TNF secretion induced by LPS, lipid A, membrane vesicles, and intact bacteria. Thus, antibody reactivity with predominantly hydrophilic elements of LPS or lipid A may not affect hydrophobic interactions between lipid A and target cell membranes necessary and sufficient for the induction of TNF. These findings raise doubts concerning the existence of true endotoxin-neutralizing antibodies.

UI MeSH Term Description Entries
D007106 Immune Sera Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen. Antisera,Immune Serums,Sera, Immune,Serums, Immune
D008050 Lipid A Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties.
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D011112 Polymyxin B A mixture of polymyxins B1 and B2, obtained from BACILLUS POLYMYXA strains. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for treatment of infections with gram-negative bacteria, but may be neurotoxic and nephrotoxic. Aerosporin,Polymyxin B Sulfate
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D012475 Salmonella A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility.
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha

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