Effects of protease inhibitors on ingestion and digestion of soluble antigen-antibody complexes by macrophages. 1982

S Nihira, and J Koyama

The inhibitory effects of diisopropyl fluorophosphate (DFP) and p-tosyl-L-lysine chloromethyl ketone (TLCK) on the ingestion and digestion of 125I-alpha-amylase [B alpha A, EC 3.2.1.1] complexed with antibody by guinea pig peritoneal macrophages were studied by sucrose density gradient fractionation. When macrophages were exposed to the complex at 37 degrees C and homogenized after washing, most of the trichloroacetic acid (TCA)-insoluble radioactivity was recovered in two fractions which behaved like the plasma membrane and lysosomes in the density gradient, and the TCA-soluble radioactivity was found in the fraction not moving into the gradient. The complex bound to Fc receptors on the cell surface, therefore, was shown to be internalized, transported to the lysosomes, and finally digested to amino acid catabolites. The inhibition with DFP caused an accumulation of the complex in a region between the plasma membrane and lysosomes. This distribution of radioactivity resembled that of cytochalasin B-inhibited macrophages. TLCK also inhibited the digestion of the complex, but the distribution of radioactivity revealed a marked accumulation of the complex in the region of lysosomes. These results provide strong support to the hypothesis that DFP blocks the ingestion of the complex, as in the case of cytochalasin B, whereas TLCK inhibits the intralysosomal proteolysis of the complex.

UI MeSH Term Description Entries
D007531 Isoflurophate A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM. DFP,Diisopropylfluorophosphate,Fluostigmine,Bis(1-methylethyl) Phosphorofluoridate,Di-isopropylphosphorofluoridate,Diisopropylphosphofluoridate,Dyflos,Floropryl,Fluorostigmine,Di isopropylphosphorofluoridate
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
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
D010447 Peptide Hydrolases Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES. Peptidase,Peptidases,Peptide Hydrolase,Protease,Proteases,Proteinase,Proteinases,Proteolytic Enzyme,Proteolytic Enzymes,Esteroproteases,Enzyme, Proteolytic,Hydrolase, Peptide
D003571 Cytochalasin B A cytotoxic member of the CYTOCHALASINS. Phomin
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000590 Amino Acid Chloromethyl Ketones Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process. Peptide Chloromethyl Ketones,Chloromethyl Ketones, Peptide,Ketones, Peptide Chloromethyl
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
D000936 Antigen-Antibody Complex The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES. Immune Complex,Antigen-Antibody Complexes,Immune Complexes,Antigen Antibody Complex,Antigen Antibody Complexes,Complex, Antigen-Antibody,Complex, Immune,Complexes, Antigen-Antibody,Complexes, Immune
D014107 Tosyllysine Chloromethyl Ketone An inhibitor of SERINE ENDOPEPTIDASES. Acts as an alkylating agent and is known to interfere with the translation process. Chlorotosylamidoaminoheptanone,TLCK,Tosyllysyl Chloromethane,Chloromethane, Tosyllysyl,Chloromethyl Ketone, Tosyllysine,Ketone, Tosyllysine Chloromethyl

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