Abstract. When paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes were exposed to H202 they lysed excessively and formed greater than normal quantities of lipid peroxides when compared to red cells of normal subjects and patients with most types of hematologic disease. It was also shown that lytic sensitivity to acidified serum was related to the enhanced lytic sensitivity to H202. If the lipid of PNH cells was first extracted then exposed to ultraviolet radiation more lipid peroxides were formed than in extracts of normal red blood cells. The possible explanations for these findings and their relationship to the PNH hemolytic mechanism are discussed.
The concept that production of a "perfect" PNH RBC, artificially, might supply information as to the nature of the defect(s) in PNH RBCs was the basis for a study in which normal RBCs were studied after preincubation in concentrated, alkaline solutions of reduced glutathione. These RBCs exhibited the following features of PNH RBCs.
1. Sensitivity to lysis by acidified serum
a. pH optimum identical to that of PNH RBCs
b. complete prevention by prior heating of serum to 56° C for 30 minutes
c. complete prevention by addition of dextran to serum
d. complete prevention by removal of magnesium ion from serum, reversed by re-addition of magnesium ion to serum
2. Positive thrombin lysis test.
3. Positive sucrose lysis test.
4. No agglutination in type-compatible serum.
5. No greater than normal agglutination in serum containing isoantibodies or elevated titers of cold agglutinins, but marked enhancement of lytic sensitivity to these antibodies, identical to that achieved with "natural" PNH cells.
6. Positive Hegglin-Maier test.
7. Decreased acetylcholinesterase activity.
8. Increased lysis and lipid peroxide formation during incubation with hydrogen peroxide.
The broad scope of these similarities permits cautious speculation that some biochemical feature(s) of PNH RBCs may have been produced in normal RBCs, artificially. The mechanism by which reduced glutathione produces the change is uncertain, but may involve either oxidation of membrane lipid or splitting of membrane protein disulfide bonds, or both.
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