Abstract
The 65 kD homologous restriction factor (HRF) was isolated from normal human erythrocytes (E) by immunoadsorption using rabbit anti-human HRF. The protein was radiolabeled and incorporated into the membrane of sheep erythrocytes (Es). Es bearing HRF exhibited a markedly reduced susceptibility to reactive lysis by C5b-9. Es-HRF with 1,000-3,000 HRF molecules per cell and sensitized with rabbit IgG anti-Es also were less susceptible to lysis by human large granular lymphocytes (LGL) than untreated Es sensitized with IgG antibody. Similarly, human E of a patient with paroxysmal nocturnal hemoglobinuria (PNH), lacking HRF and sensitized with IgG antibody underwent lysis by human LGL. Lysis was abrogated by incorporation of isolated human HRF. Incorporation of human decay-accelerating factor (DAF) into sensitized Es had no effect on antibody-dependent, cell-mediated cytotoxicity. Furthermore, lysis of Es by the isolated cytolytic C9-related protein (C9RP) of human cytotoxic lymphocytes could be inhibited by cell bound human HRF. These results suggest that HRF inhibits channel formation not only by C5b-9, but also by cytotoxic lymphocytes.
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- Gromkowski S. H., Brown T. C., Cerutti P. A., Cerottini J. C. DNA of human Raji target cells is damaged upon lymphocyte-mediated lysis. J Immunol. 1986 Feb 1;136(3):752–756. [PubMed] [Google Scholar]
- Hu V. W., Nicholson-Weller A. Enhanced complement-mediated lysis of type III paroxysmal nocturnal hemoglobinuria erythrocytes involves increased C9 binding and polymerization. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5520–5524. doi: 10.1073/pnas.82.16.5520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu C. C., Perussia B., Cohn Z. A., Young J. D. Identification and characterization of a pore-forming protein of human peripheral blood natural killer cells. J Exp Med. 1986 Dec 1;164(6):2061–2076. doi: 10.1084/jem.164.6.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Masson D., Tschopp J. Isolation of a lytic, pore-forming protein (perforin) from cytolytic T-lymphocytes. J Biol Chem. 1985 Aug 5;260(16):9069–9072. [PubMed] [Google Scholar]
- Müller-Eberhard H. J. The membrane attack complex of complement. Annu Rev Immunol. 1986;4:503–528. doi: 10.1146/annurev.iy.04.040186.002443. [DOI] [PubMed] [Google Scholar]
- Nicholson-Weller A., Burge J., Fearon D. T., Weller P. F., Austen K. F. Isolation of a human erythrocyte membrane glycoprotein with decay-accelerating activity for C3 convertases of the complement system. J Immunol. 1982 Jul;129(1):184–189. [PubMed] [Google Scholar]
- Pangburn M. K., Schreiber R. D., Müller-Eberhard H. J. Deficiency of an erythrocyte membrane protein with complement regulatory activity in paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5430–5434. doi: 10.1073/pnas.80.17.5430. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parker C. J., Wiedmer T., Sims P. J., Rosse W. F. Characterization of the complement sensitivity of paroxysmal nocturnal hemoglobinuria erythrocytes. J Clin Invest. 1985 Jun;75(6):2074–2084. doi: 10.1172/JCI111927. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Podack E. R., Young J. D., Cohn Z. A. Isolation and biochemical and functional characterization of perforin 1 from cytolytic T-cell granules. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8629–8633. doi: 10.1073/pnas.82.24.8629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenfeld S. I., Jenkins D. E., Jr, Leddy J. P. Enhanced reactive lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by C5b-9 does not involve increased C7 binding or cell-bound C3b. J Immunol. 1985 Jan;134(1):506–511. [PubMed] [Google Scholar]
- Rosenfeld S. I., Packman C. H., Jenkins D. E., Jr, Countryman J. K., Leddy J. P. Complement lysis of human erythrocytes. III. Differing effectiveness of human and guinea pig C9 on normal and paroxysmal nocturnal hemoglobinuria cells. J Immunol. 1980 Nov;125(5):2063–2068. [PubMed] [Google Scholar]
- Russell J. H. Internal disintegration model of cytotoxic lymphocyte-induced target damage. Immunol Rev. 1983;72:97–118. doi: 10.1111/j.1600-065x.1983.tb01074.x. [DOI] [PubMed] [Google Scholar]
- Schönermark S., Rauterberg E. W., Shin M. L., Löke S., Roelcke D., Hänsch G. M. Homologous species restriction in lysis of human erythrocytes: a membrane-derived protein with C8-binding capacity functions as an inhibitor. J Immunol. 1986 Mar 1;136(5):1772–1776. [PubMed] [Google Scholar]
- Shaw G. M., Levy P. C., LoBuglio A. F. Human lymphocyte, monocyte, and neutrophil antibody-dependent cell-mediated cytotoxicity toward human erythrocytes. Cell Immunol. 1978 Nov;41(1):122–133. doi: 10.1016/s0008-8749(78)80032-x. [DOI] [PubMed] [Google Scholar]
- Simone C. B., Henkart P. Permeability changes induced in erthrocyte ghost targets by antibody-dependent cytotoxic effector cells: evidence for membrane pores. J Immunol. 1980 Feb;124(2):954–963. [PubMed] [Google Scholar]
- Tschopp J., Masson D., Stanley K. K. Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis. 1986 Aug 28-Sep 3Nature. 322(6082):831–834. doi: 10.1038/322831a0. [DOI] [PubMed] [Google Scholar]
- Wåhlin B., Perlmann H., Perlmann P., Schreiber R. D., Müller-Eberhard H. J. C3 receptors on human lymphocyte subsets and recruitment of ADCC effector cells by C3 fragments. J Immunol. 1983 Jun;130(6):2831–2836. [PubMed] [Google Scholar]
- Young J. D., Cohn Z. A., Podack E. R. The ninth component of complement and the pore-forming protein (perforin 1) from cytotoxic T cells: structural, immunological, and functional similarities. Science. 1986 Jul 11;233(4760):184–190. doi: 10.1126/science.2425429. [DOI] [PubMed] [Google Scholar]
- Young J. D., Liu C. C., Leong L. G., Cohn Z. A. The pore-forming protein (perforin) of cytolytic T lymphocytes is immunologically related to the components of membrane attack complex of complement through cysteine-rich domains. J Exp Med. 1986 Dec 1;164(6):2077–2082. doi: 10.1084/jem.164.6.2077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zalman L. S., Brothers M. A., Chiu F. J., Müller-Eberhard H. J. Mechanism of cytotoxicity of human large granular lymphocytes: relationship of the cytotoxic lymphocyte protein to the ninth component (C9) of human complement. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5262–5266. doi: 10.1073/pnas.83.14.5262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zalman L. S., Brothers M. A., Müller-Eberhard H. J. A C9 related channel forming protein in the cytoplasmic granules of human large granular lymphocytes. Biosci Rep. 1985 Dec;5(12):1093–1100. doi: 10.1007/BF01119631. [DOI] [PubMed] [Google Scholar]
- Zalman L. S., Martin D. E., Jung G., Müller-Eberhard H. J. The cytolytic protein of human lymphocytes related to the ninth component (C9) of human complement: isolation from anti-CD3-activated peripheral blood mononuclear cells. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2426–2429. doi: 10.1073/pnas.84.8.2426. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zalman L. S., Wood L. M., Frank M. M., Müller-Eberhard H. J. Deficiency of the homologous restriction factor in paroxysmal nocturnal hemoglobinuria. J Exp Med. 1987 Feb 1;165(2):572–577. doi: 10.1084/jem.165.2.572. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zalman L. S., Wood L. M., Müller-Eberhard H. J. Isolation of a human erythrocyte membrane protein capable of inhibiting expression of homologous complement transmembrane channels. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6975–6979. doi: 10.1073/pnas.83.18.6975. [DOI] [PMC free article] [PubMed] [Google Scholar]