Co-clustering of denatured hemoglobin with band 3: its role in binding of autoantibodies against band 3 to abnormal and aged erythrocytes.

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Abstract
Precipitates of hemoglobin, termed Heinz bodies, occur in a fraction of erythrocytes after removal of the spleen and are also observed in aged erythrocytes. This implies that precipitates of hemoglobin might play a particular role in senescent cell recognition. By using immunofluorescence microscopy, evidence is presented in splenectomized patients and in several patients with unstable (mutant) hemoglobins that membrane-attached Heinz bodies are associated with both clusters of the anion channel, band 3, and clusters of surface-bound immunoglobulins (IgG). In 75% of the cases of unstable hemoglobin, such as sickle cell anemia or hemoglobin Koln disease, the level of cell-bound IgG (measured by 125I-labeled staphylococcal protein A) was increased severalfold above the level found in healthy controls. Immunoblot analysis identified the major fraction of cell-bound IgG to be directed to band 3. These observations indicate copolymerization of denatured hemoglobin with the cytoplasmic domain of band 3, which may cause band 3 to form clusters. These clusters probably serve as thermodynamically favored binding sites for autoantibodies in serum, which promote elimination of the erythrocytes by the immune system. Thus, erythrocytes may be removed from circulation when hemoglobin begins to denature and the cells begin to fail in their main function of oxygen transport.