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. 1997 Feb;90(2):314–322. doi: 10.1046/j.1365-2567.1997.00152.x

Monocyte-bound monoclonal antibodies inhibit the Fc gamma RI-mediated phagocytosis of sensitized red cells: the efficiency and mechanism of inhibition are determined by the nature of the antigen.

S L Shepard 1, A G Hadley 1
PMCID: PMC1456735  PMID: 9135563

Abstract

Monocyte-binding monoclonal antibodies (mAbs) inhibited the Fc gamma receptor I (Fc gamma RI)-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-Fc gamma RI 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 Fc gamma RI-mediated phagocytosis that involved the cross-linking of a proportion of Fc gamma RI (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 Fc gamma RI-mediated interactions with E-IgG in a manner that did not involve IgG (Fc) crosslinking or blockade of Fc gamma RI. In this respect, Fc gamma RI-mediated phagocytosis was more susceptible to inhibition than receptor-mediated adherence.

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Selected References

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  1. Brown E. J., Bohnsack J. F., Gresham H. D. Mechanism of inhibition of immunoglobulin G-mediated phagocytosis by monoclonal antibodies that recognize the Mac-1 antigen. J Clin Invest. 1988 Feb;81(2):365–375. doi: 10.1172/JCI113328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown E. J. Complement receptors and phagocytosis. Curr Opin Immunol. 1991 Feb;3(1):76–82. doi: 10.1016/0952-7915(91)90081-b. [DOI] [PubMed] [Google Scholar]
  3. Camp R. L., Kraus T. A., Puré E. Variations in the cytoskeletal interaction and posttranslational modification of the CD44 homing receptor in macrophages. J Cell Biol. 1991 Dec;115(5):1283–1292. doi: 10.1083/jcb.115.5.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clarkson S. B., Bussel J. B., Kimberly R. P., Valinsky J. E., Nachman R. L., Unkeless J. C. Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody. N Engl J Med. 1986 May 8;314(19):1236–1239. doi: 10.1056/NEJM198605083141907. [DOI] [PubMed] [Google Scholar]
  5. Clarkson S. B., Kimberly R. P., Valinsky J. E., Witmer M. D., Bussel J. B., Nachman R. L., Unkeless J. C. Blockade of clearance of immune complexes by an anti-Fc gamma receptor monoclonal antibody. J Exp Med. 1986 Aug 1;164(2):474–489. doi: 10.1084/jem.164.2.474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Damjanovich S., Vereb G., Schaper A., Jenei A., Matkó J., Starink J. P., Fox G. Q., Arndt-Jovin D. J., Jovin T. M. Structural hierarchy in the clustering of HLA class I molecules in the plasma membrane of human lymphoblastoid cells. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1122–1126. doi: 10.1073/pnas.92.4.1122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davies A., Lachmann P. J. Membrane defence against complement lysis: the structure and biological properties of CD59. Immunol Res. 1993;12(3):258–275. doi: 10.1007/BF02918257. [DOI] [PubMed] [Google Scholar]
  8. Davis W., Harrison P. T., Hutchinson M. J., Allen J. M. Two distinct regions of FC gamma RI initiate separate signalling pathways involved in endocytosis and phagocytosis. EMBO J. 1995 Feb 1;14(3):432–441. doi: 10.1002/j.1460-2075.1995.tb07019.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Daëron M., Malbec O., Latour S., Arock M., Fridman W. H. Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors. J Clin Invest. 1995 Feb;95(2):577–585. doi: 10.1172/JCI117701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dooren M. C., Kuijpers R. W., Joekes E. C., Huiskes E., Goldschmeding R., Overbeeke M. A., von dem Borne A. E., Engelfriet C. P., Ouwehand W. H. Protection against immune haemolytic disease of newborn infants by maternal monocyte-reactive IgG alloantibodies (anti-HLA-DR). Lancet. 1992 May 2;339(8801):1067–1070. doi: 10.1016/0140-6736(92)90661-l. [DOI] [PubMed] [Google Scholar]
  11. Duchemin A. M., Ernst L. K., Anderson C. L. Clustering of the high affinity Fc receptor for immunoglobulin G (Fc gamma RI) results in phosphorylation of its associated gamma-chain. J Biol Chem. 1994 Apr 22;269(16):12111–12117. [PubMed] [Google Scholar]
  12. Edidin M., Stroynowski I. Differences between the lateral organization of conventional and inositol phospholipid-anchored membrane proteins. A further definition of micrometer scale membrane domains. J Cell Biol. 1991 Mar;112(6):1143–1150. doi: 10.1083/jcb.112.6.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Elemer G. S., Edgington T. S. Microfilament reorganization is associated with functional activation of alpha M beta 2 on monocytic cells. J Biol Chem. 1994 Feb 4;269(5):3159–3166. [PubMed] [Google Scholar]
  14. Graham I. L., Gresham H. D., Brown E. J. An immobile subset of plasma membrane CD11b/CD18 (Mac-1) is involved in phagocytosis of targets recognized by multiple receptors. J Immunol. 1989 Apr 1;142(7):2352–2358. [PubMed] [Google Scholar]
  15. Griffiths H. L., Kumpel B. M., Elson C. J., Hadley A. G. The functional activity of human monocytes passively sensitized with monoclonal anti-D suggests a novel role for Fc gamma RI in the immune destruction of blood cells. Immunology. 1994 Nov;83(3):370–377. [PMC free article] [PubMed] [Google Scholar]
  16. Kuijpers R. W., Dooren M. C., von dem Borne A. E., Ouwehand W. H. Detection of human monocyte-reactive alloantibodies by flow cytometry after selective downmodulation of the Fc receptor I. Blood. 1991 Oct 15;78(8):2150–2156. [PubMed] [Google Scholar]
  17. Kumpel B. M., Hadley A. G. Functional interactions of red cells sensitized by IgG1 and IgG3 human monoclonal anti-D with enzyme-modified human monocytes and FcR-bearing cell lines. Mol Immunol. 1990 Mar;27(3):247–256. doi: 10.1016/0161-5890(90)90137-o. [DOI] [PubMed] [Google Scholar]
  18. Kumpel B. M., Poole G. D., Bradley B. A. Human monoclonal anti-D antibodies. I. Their production, serology, quantitation and potential use as blood grouping reagents. Br J Haematol. 1989 Jan;71(1):125–129. doi: 10.1111/j.1365-2141.1989.tb06285.x. [DOI] [PubMed] [Google Scholar]
  19. Kurlander R. J. Blockade of Fc receptor-mediated binding to U-937 cells by murine monoclonal antibodies directed against a variety of surface antigens. J Immunol. 1983 Jul;131(1):140–147. [PubMed] [Google Scholar]
  20. Kávai M., Gyimesi E., Szücs G., Szegedi G. Binding and endocytosis of erythrocytes sensitized with rabbit IgG via Fc gamma receptors of human monocytes. Immunology. 1991 Dec;74(4):657–660. [PMC free article] [PubMed] [Google Scholar]
  21. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  22. Lloyd-Evans P., Kumpel B. M., Bromelow I., Austin E., Taylor E. Use of a directly conjugated monoclonal anti-D (BRAD-3) for quantification of fetomaternal hemorrhage by flow cytometry. Transfusion. 1996 May;36(5):432–437. doi: 10.1046/j.1537-2995.1996.36596282587.x. [DOI] [PubMed] [Google Scholar]
  23. Majima T., Ohashi Y., Nagatomi R., Iizuka A., Konno T. Defective mononuclear cell antibody-dependent cellular cytotoxicity (ADCC) in patients with leukocyte adhesion deficiency emphasizing on different CD11/CD18 requirement of Fc gamma RI versus Fc gamma RII in ADCC. Cell Immunol. 1993 May;148(2):385–396. doi: 10.1006/cimm.1993.1120. [DOI] [PubMed] [Google Scholar]
  24. Neppert J., Marquard F., Mueller-Eckhardt C. Murine monoclonal antibodies and human alloantisera specific for HLA inhibit monocyte phagocytosis of anti-D-sensitized human red blood cells. Eur J Immunol. 1985 Jun;15(6):559–563. doi: 10.1002/eji.1830150606. [DOI] [PubMed] [Google Scholar]
  25. Newland A. C., Macey M. G. Immune thrombocytopenia and Fc receptor-mediated phagocyte function. Ann Hematol. 1994 Aug;69(2):61–67. doi: 10.1007/BF01698483. [DOI] [PubMed] [Google Scholar]
  26. Nicholson-Weller A., Wang C. E. Structure and function of decay accelerating factor CD55. J Lab Clin Med. 1994 Apr;123(4):485–491. [PubMed] [Google Scholar]
  27. O'Grady J. H., Looney R. J., Anderson C. L. The valence for ligand of the human mononuclear phagocyte 72 kD high-affinity IgG Fc receptor is one. J Immunol. 1986 Oct 1;137(7):2307–2310. [PubMed] [Google Scholar]
  28. Ohta Y., Stossel T. P., Hartwig J. H. Ligand-sensitive binding of actin-binding protein to immunoglobulin G Fc receptor I (Fc gamma RI). Cell. 1991 Oct 18;67(2):275–282. doi: 10.1016/0092-8674(91)90179-3. [DOI] [PubMed] [Google Scholar]
  29. Osborne J. M., Chacko G. W., Brandt J. T., Anderson C. L. Ethnic variation in frequency of an allelic polymorphism of human Fc gamma RIIA determined with allele specific oligonucleotide probes. J Immunol Methods. 1994 Aug 1;173(2):207–217. doi: 10.1016/0022-1759(94)90299-2. [DOI] [PubMed] [Google Scholar]
  30. Pfefferkorn L. C., van de Winkel J. G., Swink S. L. A novel role for IgG-Fc. Transductional potentiation for human high affinity Fc gamma receptor (Fc gamma RI) signaling. J Biol Chem. 1995 Apr 7;270(14):8164–8171. doi: 10.1074/jbc.270.14.8164. [DOI] [PubMed] [Google Scholar]
  31. Shepard S. L., Noble A. L., Filbey D., Hadley A. G. Inhibition of the monocyte chemiluminescent response to anti-D-sensitized red cells by Fc gamma RI-blocking antibodies which ameliorate the severity of haemolytic disease of the newborn. Vox Sang. 1996;70(3):157–163. doi: 10.1111/j.1423-0410.1996.tb01315.x. [DOI] [PubMed] [Google Scholar]
  32. Takai T., Li M., Sylvestre D., Clynes R., Ravetch J. V. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell. 1994 Feb 11;76(3):519–529. doi: 10.1016/0092-8674(94)90115-5. [DOI] [PubMed] [Google Scholar]
  33. Tax W. J., Willems H. W., Reekers P. P., Capel P. J., Koene R. A. Polymorphism in mitogenic effect of IgG1 monoclonal antibodies against T3 antigen on human T cells. Nature. 1983 Aug 4;304(5925):445–447. doi: 10.1038/304445a0. [DOI] [PubMed] [Google Scholar]
  34. Wade W. F., Freed J. H., Edidin M. Translational diffusion of class II major histocompatibility complex molecules is constrained by their cytoplasmic domains. J Cell Biol. 1989 Dec;109(6 Pt 2):3325–3331. doi: 10.1083/jcb.109.6.3325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Woof J. M., Partridge L. J., Jefferis R., Burton D. R. Localisation of the monocyte-binding region on human immunoglobulin G. Mol Immunol. 1986 Mar;23(3):319–330. doi: 10.1016/0161-5890(86)90059-3. [DOI] [PubMed] [Google Scholar]
  36. Ziegler-Heitbrock H. W., Ulevitch R. J. CD14: cell surface receptor and differentiation marker. Immunol Today. 1993 Mar;14(3):121–125. doi: 10.1016/0167-5699(93)90212-4. [DOI] [PubMed] [Google Scholar]
  37. van de Winkel J. G., Anderson C. L. Biology of human immunoglobulin G Fc receptors. J Leukoc Biol. 1991 May;49(5):511–524. doi: 10.1002/jlb.49.5.511. [DOI] [PubMed] [Google Scholar]

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