Monocyte‐bound monoclonal antibodies inhibit the FcγRI‐mediated phagocytosis of sensitized red cells: the efficiency and mechanism of inhibition are determined by the nature of the antigen
Monocyte‐binding monoclonal antibodies (mAbs) inhibited the Fcγ receptor I (FcγRI)‐mediated phagocytosis of red cells sensitized with human monoclonal immunoglobulin G (IgG) anti‐D (E‐IgG) via three distinct mechanisms depending on their specificity. First, all monocyte‐binding mAbs tested inhibited...
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Published in | Immunology Vol. 90; no. 2; pp. 314 - 322 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.02.1997
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Subjects | |
Online Access | Get full text |
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Summary: | Monocyte‐binding monoclonal antibodies (mAbs) inhibited the Fcγ receptor I (FcγRI)‐mediated phagocytosis of red cells sensitized with human monoclonal immunoglobulin G (IgG) anti‐D (E‐IgG) via three distinct mechanisms depending on their specificity. First, all monocyte‐binding mAbs tested inhibited the adherence (and hence the phagocytosis) of E‐IgG. They also inhibited the binding of fluorescein isothiocyanate (FITC) conjugated IgG anti‐D. This inhibition of ligand binding was more efficiently promoted by murine (m) IgG2a than mIgG1 mAbs and presumably involved receptor blockade via the formation of antigen (Ag)–mAb–FcγRI complexes on the monocyte membrane. Monocytes passively sensitized with human monoclonal anti‐D (M‐IgG) were used in experiments to distinguish between inhibition of ligand binding and inhibition of phagocytosis. In this way, it was shown that mAbs to transmembrane molecules (CD11b/CD18, CD44, and HLA) inhibited the phagocytosis of red cells adherent to M‐IgG. Under the same conditions, mAbs to glycosylphosphatidylinositol (GPI) linked molecules (CD14, CD55 and CD59) did not inhibit phagocytosis. These data suggested a second mechanism of inhibition of FcγRI‐mediated phagocytosis that involved the cross‐linking of a proportion of FcγRI (i.e. those not ligated with IgG anti‐D) to molecules which are relatively constrained in the cell membrane. A third mechanism of inhibition was revealed by the use of F(ab′)2 fragments of mAb to CD11b which inhibited FcγRI‐mediated interactions with E‐IgG in a manner that did not involve IgG (Fc) crosslinking or blockade of FcγRI. In this respect, FcγRI‐mediated phagocytosis was more susceptible to inhibition than receptor‐mediated adherence. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0019-2805 1365-2567 |
DOI: | 10.1046/j.1365-2567.1997.00152.x |