Hemoglobin and heme scavenging.
Release of hemoglobin into plasma is a physiological phenomenon associated with intravascular hemolysis. In plasma, stable haptoglobin-hemoglobin complexes are formed and these are subsequently delivered to the reticulo-endothelial system by CD163 receptor-mediated endocytosis. Heme arising from the degradation of hemoglobin, myoglobin, and of enzymes with heme prosthetic groups could be delivered in plasma. Albumin, haptoglobin, hemopexin, and high and low density lipoproteins cooperate to trap the plasma heme, thereby ensuring its complete clearance. Then hemopexin releases the heme into hepatic parenchymal cells only after internalization of the hemopexin-heme complex by CD91 receptor-mediated endocytosis. Moreover, alpha1-microglobulin contributes to heme degradation by a still unknown mechanism, with the concomitant formation of heterogeneous yellow-brown kynurenine-derived chromophores which are very tightly bound to amino acid residues close to the rim of the lipocalin pocket. During hemoglobin synthesis, the erythroid alpha-chain hemoglobin-stabilizing protein specifically binds free alpha-hemoglobin subunits limiting the free protein toxicity. Although highly toxic because capable of catalyzing free radical formation, heme is also a major and readily available source of iron for pathogenic organisms. Gram-negative bacteria pick up the heme-bound iron through the secretion of a hemophore that takes up either free heme or heme bound to heme-proteins and transports it to a specific receptor, which, in turn, releases the heme and hence iron into the bacterium. Here, hemoglobin and heme trapping mechanisms are summarized.
Ascenzi
Paolo
P
National Institute for Infectious Diseases IRCCS 'Lazzaro Spallanzani', Roma, Italy. ascenzi@uniroma3.it
Bocedi
Alessio
A
Visca
Paolo
P
Altruda
Fiorella
F
Tolosano
Emanuela
E
Beringhelli
Tiziana
T
Fasano
Mauro
M
D000818:Animals; D006242:Haptoglobins / Q000502:physiology; D006418:Heme / Q000378:metabolism*; D006454:Hemoglobins / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D014360:Trypsin Inhibitor, Kunitz Soybean
D006242:Haptoglobins; D006454:Hemoglobins; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human; D006418:Heme; D014360:Trypsin Inhibitor, Kunitz Soybean