title: Degradation of glycophorin A of human erythrocytes in patients with myelo- or lymphoproliferative disorders: possible role of neutrophil proteases.
abstract: We have previously reported that glycophorin A (GPA) of human erythrocytes (carrying blood group M and N determinants) was totally digested by incubation of erythrocytes with human neutrophil elastase (HNE) and cathepsin G (CathG). The membrane-bound GPA fragments fractionated by SDS-PAGE gave characteristic patterns of bands detected by immunoblotting with the monoclonal antibody PEP80. Erythrocytes were incubated with HNE and CathG at low enzyme concentrations, similar to those found in vivo. Characteristic electrophoretic patterns of bands derived from a partial GPA digestion were observed and these patterns were different for both enzymes and different from those obtained after total GPA digestion. GPA was also partially digested by incubation of erythrocytes with granulocytes in the presence of Ca2+ and calcium ionophore and electrophoretic pattern of digestion products was similar to that obtained with low doses of HNE. No GPA digestion products were detected after treatment of erythrocytes with plasmin and kallikrein. Untreated erythrocytes of 21 patients with various myelo- or lymphoproliferative disorders were tested by SDS-PAGE of RBC membranes and immunoblotting with the anti-GPA PEP80 antibody. GPA degradation products, resembling those formed by a mild CathG treatment of control RBC, were detected in nine patients. GPA fragmentation was in some cases accompanied by a reduced expression of blood group MN determinants. No distinct relation was observed between the occurrence of GPA degradation in erythrocytes and increases in plasma concentrations of HNE-alpha1-proteinase inhibitor (alpha1-PI) complex considered to be an indication of a release of neutrophil proteinases in vivo. However, the results suggested that a partial GPA degradation in haematological proliferative disorders may occur due to limited proteolysis by neutrophil proteinases, most likely by CathG.
authors.affiliation: Institute of Haematology and Blood Transfusion, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Bykowska
authors.forename: M
authors.initials: M
authors.lastname: Duk
authors.forename: G
authors.initials: G
authors.lastname: Kuśnierz-Alejska
authors.forename: A
authors.initials: A
authors.lastname: Sikorska
authors.forename: M
authors.initials: M
authors.lastname: Letowska
authors.forename: E
authors.initials: E
authors.lastname: Mendek-Czajkowska
authors.forename: S
authors.initials: S
authors.lastname: Lopaciuk
authors.forename: M
authors.initials: M
authors.lastname: Kopeç
authors.forename: E
authors.initials: E
authors.lastname: Lisowska
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006021:Glycophorins / Q000378:metabolism*; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000201:enzymology*; D009504:Neutrophils / Q000201:enzymology*; D012697:Serine Endopeptidases
chemical_list: D006021:Glycophorins; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase