title: Differential susceptibility of type III erythrocytes of paroxysmal nocturnal hemoglobinuria to lysis mediated by complement and perforin.
abstract: Previous reports have suggested that a 65 kDa membrane protein, termed homologous restriction factor (HRF), in addition to protecting erythrocytes (E) against lysis by homologous complement (C), may also be involved in protecting cytolytic lymphocytes against lysis mediated by a pore-forming protein (PFP/perforin), one of their own lytic mediators. Here, we used HRF-deficient type III E of patients with paroxysmal nocturnal hemoglobinuria (PNH) to study their susceptibility to lysis mediated by homologous C and perforin, and compared it with lysis of HRF-bearing control or PNH type I E. We show that type III E of PNH patients are indeed more susceptible to lysis mediated by homologous C than control or type I E, but they are as susceptible to perforin-mediated lysis as type I E. In addition, all human E (type I or III) tested here are equally susceptible to lysis mediated by either human (homologous) or murine (heterologous) perforin. By immunoblot analysis, we confirm that type III E, in contrast to type I E, were deficient in the 65 kDa HRF. These results support the notion that homologous species restriction is seen in the C- but not in the lymphocyte perforin-system and argue against an active participation of HRF in protecting cells from perforin-mediated lysis.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York 10021.
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.forename: P M
authors.initials: PM
authors.lastname: Persechini
authors.forename: W F
authors.initials: WF
authors.lastname: Rosse
authors.forename: B
authors.initials: B
authors.lastname: Perussia
authors.forename: J D
authors.initials: JD
authors.lastname: Young
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001798:Blood Proteins / Q000032:analysis; D018957:CD59 Antigens; D002352:Carrier Proteins; D003165:Complement System Proteins / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000032:analysis; D004913:Erythrocytes, Abnormal / Q000032:analysis / Q000145:classification* / Q000276:immunology; D006168:Guinea Pigs; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000276:immunology; D006461:Hemolysis; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins
chemical_list: D001798:Blood Proteins; D018957:CD59 Antigens; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; C051590:CD59 protein, human; D054353:Perforin; D003165:Complement System Proteins