Role of Hemoglobin Denaturation and Band 3 Clustering in Initiating Red Cell Removal
While multiple mechanisms likely exist to assure that a defective erythrocyte does not escape removal by macrophages, we believe that the more heavily used clearance pathways will have certain characteristics in common. First, the pathway should involve a change in components already present in the circulating erythrocytes, since de novo protein synthesis will have terminated before the erythrocyte reaches maturity. Second, the changes initiating the removal sequence must eventually be manifested on the exofacial surface of the cell, since a macrophage has little means of detecting an intracellular biochemical lesion. And finally, the exofacial changes recognized by the macrophage must be inducible by a change in the biochemistry of the cytoplasm, since cells that develop intracellular defects early in their lifespans are also removed early (e.g., sickle cells, (1) ß-thalassemic cells, (2) cells with enzyme deficiencies, (3) cells treated with oxidants, (4) etc). That is, a linkage of some sort must exist between the functional state of components in the cytoplasm and markers at the cell surface recognized by macrophages. The hypothesis outlined below describes how hemoglobin, the most abundant protein in the cytoplasm, and band 3, the most prominent protein in the membrane cooperate to establish this linkage, transducing information regarding the biochemical integrity of the cell to the reticuloendothelial system which is responsible for aged/abnormal cell clearance.
KeywordsSickle Cell Human Erythrocyte Complement Fixation Cluster Agent Globin Chain
Unable to display preview. Download preview PDF.
- 7.P. S. Low, Interaction of native and denatured hemoglobins with band 3: consequences for erythrocytes structure and function, in “Red Blood Cell Membranes” P. Agre and J. C. Parker, ed., Marcel Dekker, Inc. NY, p. 237 (1989).Google Scholar
- 8.P. S. Low and R. Kannan, Effect of hemoglobin denaturation on membrane strucutre and IgG binding: role in red cell aging, in “The Red Cell: Seventh Ann Arbor Conference”, Alan R. Liss, Inc. p. 525 (1989).Google Scholar
- 12.P. Hochstein and S. K. Jain, Association of lipid peroxidation and polymerization of membrane proteins with erythrocyte aging, FASEB 40:183 (1981).Google Scholar
- 14.F. Turrini, A. Naitana, L. Mannuzzu, G. P. Pescarmona and P. Arese, Increased red cell calcium, decreased calcium adenosine triphosphatase, and altered membrane proteins during Fava bean hemolysis in glucose-6-phosphate dehydrogenase-deficient (Mediterranean variant) individuals, Blood 66:302 (1985).PubMedGoogle Scholar
- 18.M. M. B. Kay, K. Sorensen, P. Wong and P. Bolton, Antigenicity, storage and aging: physiologic autoantibodies to cell membrane and serum proteins and the senescent cell antigen, Molec. and Cell. Biochem. 49:65 (1982).Google Scholar
- 33.D. Aminoff, M. A. Ghalambor and C.J. Henrich, GOST, galactose oxidase and sialyl transferase, substrate and receptor sites in erythrocyte senescence, in “Erythrocyte Membranes 2. Recent Clinical and Experimental Advances”, W. C. Kruckerberg, J. W. Eaton and G. J. Brewer, ed., Liss: New York, p. 269 (1981).Google Scholar
- 40.F. Turrini, P. Arese, J. Yuan and P. S. Low, Clustering of integral membrane proteins of the human erythrocyte membrane stimulates autologous IgG binding, complement deposition and phagocytosis, submitted for publication (1991).Google Scholar
- 42.R. Kannan, Mechanism of aging of human red cells, Ph. D. Dissertation, Purdue University, 71 (1990).Google Scholar
- 43.R. Kannan, J. Yuan and P. S. Low, Isolation and characterization of antibody-enriched complexes from membranes of density fractionated human erythrocytes, manuscript submitted (1991).Google Scholar
- 49.H. U. Lutz, A naturally occurring autoantibody to band 3 protein of human red blood cells and its possible role in removal of senescent red cells, in “Red Cell Membrane Glycoconjugates and Related Genetic Markers”, J-P Cartron, P. Rouger and C. Salmon, eds., p. 273 (1983).Google Scholar
- 54.N. Yousaf, J. C. Howard and B. D. Williams, Studies in the rat of antibody-sensitized and N-ethylmaleimide-treated erythrocyte clearance by the liver: effects of immune complex infusion and complement activation, Immunolgy 64:193 (1988).Google Scholar