Band 3/complement-mediated recognition and removal of normally senescent and pathological human erythrocytes.
Band 3 modifications that normally occur during physiological red blood cell (RBC) senescence in humans, and occasionally in pathological conditions are described in the context of their role in enhancing RBC recognition and phagocytic removal. Band 3 modifications are mostly due to oxidative insults that gradually accumulate during the RBC lifespan or impact massively in a shorter time period in pathological conditions. The oxidative insults that impact on the RBC, the protective mechanisms that counteract those damages and the phenotypic modifications that accumulate during the RBC lifespan are described. It is shown how specific oxidative as well as non-oxidative band 3 modifications enhance RBC membrane affinity for normally circulating anti-band 3 antibodies, and how membrane-bound anti-band 3 antibodies bring about a limited complement activation and membrane deposition of complement C3 fragments. The partially covalent complexes between anti-band 3 antibodies and complement C3 fragments are very powerful opsonins readily recognized by the CR1 complement receptor on the phagocyte. Band 3 modifications typically encountered in old RBCs have crystallized to a number of band 3-centered models of RBC senescence. One of those band 3-centered models, the so-called 'band 3/complement RBC removal model' first put up by Lutz et al. is discussed in more detail. Finally, it is shown how the genetic deficiency of glucose-6-phosphate dehydrogenase (G6PD) plus fava bean consumption, and a widespread RBC parasitic disease, P. falciparum malaria, may lead to massive and rapid destruction of RBCs by a mechanism comparable to a dramatic, time-compressed enhancement of normal RBC senescence.
Arese
Paolo
P
Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Torino. paolo.arese@unito.it
Turrini
Franco
F
Schwarzer
Evelin
E
D001457:Anion Exchange Protein 1, Erythrocyte / Q000737:chemistry / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism; D004905:Erythrocyte Aging / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D005236:Favism / Q000097:blood; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood; D006418:Heme / Q000378:metabolism; D006420:Hemeproteins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism; D016778:Malaria, Falciparum / Q000097:blood; D008954:Models, Biological; D017463:Receptors, Complement 3b / Q000378:metabolism
D001457:Anion Exchange Protein 1, Erythrocyte; D006420:Hemeproteins; D017463:Receptors, Complement 3b; C001332:hemichrome; D006418:Heme; D003179:Complement C3b; D007501:Iron; D005954:Glucosephosphate Dehydrogenase