Proteolysis induces increased binding affinity of the monocyte type II FcR for human IgG. 1989

J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
Department of Medicine, University Hospital Nijmegen, The Netherlands.

Human monocytes express two types of IgG FcR, Fc gamma RI and Fc gamma RII. These can be assayed by using indicator E sensitized by human IgG (EA-human IgG) or mouse IgG1, (EA-mouse IgG1), respectively. On mouse macrophages, Fc gamma RI is sensitive to trypsin, whereas Fc gamma RII is trypsin resistant. We studied the effects of the proteolytic enzymes pronase and trypsin on human monocyte Fc gamma R. Neither enzyme caused a decrease in rosetting mediated by monocyte Fc gamma RI. Human Fc gamma RII is polymorphic, and monocytes interact either strongly or weakly with mouse IgG1. The interaction of low responder monocytes with mouse IgG1 was dramatically increased (to the level exhibited by high responder monocytes) by protease treatment. The effects of proteases on Fc gamma RII were investigated in more detail by using monocytes from which Fc gamma RI was selectively modulated by using immobilized immune complexes. Proteolysis of such modulated monocytes induced an increased interaction with EA-human IgG. Fc gamma RII appears to mediate this interaction. This conclusion is supported by the observation that after proteolysis, the Fc gamma RII-mediated binding of EA-mouse IgG1 becomes susceptible to inhibition by (monomeric) human IgG. To quantify the effect of proteolytic enzymes on Fc gamma RII, we performed binding studies with cell line K562, that expresses only Fc gamma RII. A significant increase in Ka of Fc gamma RII for dimeric human IgG complexes was observed when K562 cells were treated with protease. To elucidate the mechanism of this enhancement of Ka by proteolysis, we performed immunoprecipitation studies. Neither m.w., nor IEF pattern of Fc gamma RII were influenced by proteolysis. Moreover, the expression of Fc gamma RII was not affected by proteolysis as evidenced by immunofluorescence studies and Scatchard analysis, and neither were Fc gamma RI or Fc gamma RIII induced. We conclude that proteolysis increases the affinity of Fc gamma RII for human IgG, and speculate that such a proteolysis-induced change may also occur in vivo, e.g., at inflammatory sites.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007525 Isoelectric Focusing Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point. Electrofocusing,Focusing, Isoelectric
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
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
D011961 Receptors, Fc Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules. Fc Receptors,Fc Receptor,Receptor, Fc
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D004915 Leukemia, Erythroblastic, Acute A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood. Di Guglielmo's Disease,Erythremic Myelosis,Erythroblastic Leukemia, Acute,Erythroleukemia,Leukemia, Myeloid, Acute, M6,Myeloid Leukemia, Acute, M6,Di Guglielmo Disease,Acute Erythroblastic Leukemia,Acute Erythroblastic Leukemias,Di Guglielmos Disease,Disease, Di Guglielmo,Disease, Di Guglielmo's,Erythremic Myeloses,Erythroblastic Leukemias, Acute,Erythroleukemias,Leukemia, Acute Erythroblastic,Leukemias, Acute Erythroblastic,Myeloses, Erythremic,Myelosis, Erythremic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
July 2023, Cell reports,
J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
February 1997, Journal of immunology (Baltimore, Md. : 1950),
J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
September 1984, Journal of immunology (Baltimore, Md. : 1950),
J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
October 1989, Experimental neurology,
J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
May 1998, Journal of biochemistry,
J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
August 1982, Immunology,
J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
November 1985, Clinical immunology and immunopathology,
J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
April 1988, Nature,
J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
January 1989, Immunology,
J G van de Winkel, and R van Ommen, and T W Huizinga, and M A de Raad, and W B Tuijnman, and P J Groenen, and P J Capel, and R A Koene, and W J Tax
January 1986, European journal of immunology,
Copied contents to your clipboard!