Glycophorin A-mediated haemolysis of normal human erythrocytes: evidence for antigen aggregation in the pathogenesis of immune haemolysis.
The inexplicable severity of anti-Pr autoimmune haemolytic anaemia led us to test the hypothesis that the haemolysis was primarily due to a change in the function of glycophorin A, on which the Pr antigen is located. The lectins Maclura pomifera and wheat germ agglutinin that bind to glycophorin A induced the haemolysis of normal erythrocytes in vitro. Lectin binding led to an increase in erythrocyte membrane permeability to sodium and potassium, the former resulting in an influx of water and subsequent haemolysis. The response was glycophorin A specific as Concanavalin A, which binds to band 3, did not cause haemolysis and peanut agglutinin only did so after removal of erythrocyte sialic acid. The lectin-induced cation leak was not mediated by activation of cation channels as the inhibitors, tetrodotoxin, amiloride and 4,4' disothiocyanate stilbene 2,2'disulphonate, had no effect, suggesting that the haemolysis was due to exacerbation of the inherent cation permeability of the erythrocyte membrane. A human IgAK anti-Pr autoantibody and a mouse anti-human glycophorin A antibody increased erythrocyte permeability to sodium. The role of glycophorin A in stabilizing and, upon aggregation, destabilizing the phospholipid bilayer is discussed. Our findings may help explain the severity of anti-Pr autoimmune haemolytic anaemia and other pathophysiological changes in human erythrocytes.
Brain
Michael C
MC
Department of Medicine, Faculty of Medicine, University of Calgary, Canada. brain@ucalgary.ca
Prevost
Jay M
JM
Pihl
Carin E
CE
Brown
Christopher B
CB
D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood* / Q000276:immunology; D018929:Cell Culture Techniques; D002463:Cell Membrane Permeability; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D006021:Glycophorins / Q000502:physiology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009995:Osmosis; D010042:Ouabain / Q000494:pharmacology; D037121:Plant Lectins / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology; D014909:Wheat Germ Agglutinins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006021:Glycophorins; D037121:Plant Lectins; D014909:Wheat Germ Agglutinins; C034551:maclurin; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium