Mechanism of enhanced complement-dependent cytotoxicity of papain-treated lymphocytes: evidence for increased stability of classical pathway C3 convertase.
The mechanisms of enhanced antibody-mediated, complement-dependent cytotoxicity caused by proteolytic treatment of cells was studied in a model system based on HLA microlymphocytotoxicity methods. In this model, papain treatment of lymphocytes resulted in a) no change in antibody binding, b) a slight decrease in initial binding of C4, c) a marked increase in stability of cell-bound C4b, resulting in d) an increase of cell-bound C3, and e) no increase in lytic efficiency of the C5b-9 membrane attack complex. We conclude that the most important step in papain enhancement of lysis of lymphocytes is an increased stability of cell-bound C4b, possibly through decreased surface binding of C4-bp. This mechanism may be relevant to the pathologically increased lysis of cells occurring in patients with hereditary erythroblastic multinuclearity with a positive acidified-serum test (HEM-PAS).
D000742:Anemia, Dyserythropoietic, Congenital / Q000276:immunology; D000818:Animals; D003176:Complement C3 / Q000276:immunology; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003181:Complement C4 / Q000276:immunology; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D010206:Papain / Q000494:pharmacology*; D011817:Rabbits; D012756:Sheep
D003176:Complement C3; D003181:Complement C4; D006680:HLA Antigens; D003165:Complement System Proteins; D050577:Complement C3-C5 Convertases; D010206:Papain