title: Expression of rat complement control protein Crry on tumor cells inhibits rat natural killer cell-mediated cytotoxicity.
abstract: Crry is a rodent membrane-bound inhibitor of complement activation and is a structural and functional analog of the human complement inhibitors decay-accelerating factor and membrane cofactor protein. We found previously that expression of rat Crry on a human tumor cell line enhances tumorigenicity in nude rats. In this study, we investigated the effect that rat Crry expressed on tumor cells has on rat cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). The expression of rat Crry on the surface of different human tumor cell lines inhibited ADCC mediated by rat natural killer (NK) cells. C3 opsonization is known to enhance NK cell-mediated cytolysis, and a potential mechanism for Crry-mediated inhibition of NK cell lysis is through Crry modulation of C3 deposition on target cells. However, the transfection of tumor cell lines with Crry enhanced their resistance to NK cell-mediated lysis in the absence of exogenous complement. The resistance of Crry-expressing tumor cells to NK cell-mediated ADCC could be reversed by treatment with anti-Crry F(ab)(2). In addition, anti-Crry F(ab)(2) enhanced the susceptibility of 13762 rat mammary adenocarcinoma cells (that endogenously express Crry) to ADCC mediated by allogeneic rat NK cells in the absence of added complement. We found no evidence that rat NK cells were a source of complement for target cell deposition during the in vitro cytolysis assay. These data suggest a novel function for rat Crry in tumor immune surveillance that may be unrelated to complement inhibition.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Caragine
authors.forename: Masaki
authors.initials: M
authors.lastname: Imai
authors.forename: Alan B
authors.initials: AB
authors.lastname: Frey
authors.forename: Stephen
authors.initials: S
authors.lastname: Tomlinson
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000954:Antigens, Surface / Q000276:immunology; D001943:Breast Neoplasms / Q000473:pathology; D018957:CD59 Antigens / Q000235:genetics; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D006239:Haplotypes; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology; D009895:Opsonin Proteins / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000235:genetics / Q000502:physiology*; D017463:Receptors, Complement 3b; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D018957:CD59 Antigens; D003176:Complement C3; C081470:Cr1l protein, mouse; C513105:Cr1l protein, rat; D007140:Immunoglobulin Fab Fragments; D009895:Opsonin Proteins; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011993:Recombinant Fusion Proteins; D003165:Complement System Proteins