Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification

The Staphylococcus aureus Protein IsdH Inhibits Host Hemoglobin Scavenging to Promote Heme Acquisition by the Pathogen

“…The molecular mass of IsdH N1 determined by SEC-RALS in solution (18.6 kDa) was close to the monomer molecular mass based on sequence and determined by mass spectrometry (18,907 Da) (Fig. 3).…”

“…Hb released into human plasma during hemolysis binds rapidly to plasma Hp, which protects against the highly oxidative and toxic properties of Hb by direct shielding of oxidative spots (15,16) and by the promotion of Hb-uptake via the macrophage-specific endocytic receptor CD163 (17)(18)(19)(20)(21). Hp exists in three main variants designated Hp1-1, Hp2-1, and Hp2-2, where Hp1-1 is a Hp dimer, whereas the two other variants are found as different multimeric forms.…”

Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies

“…These protective functions appear to be related to the ability of Hp to firmly stabilize the structure of the bound Hb ab dimers, and to a less understood mechanism whereby Hp shields peroxidative reactions within the Hb-Hp complex from external substrates. The Hb -Hp complex can still react with many ligands such as O 2 , NO, H 2 O 2 , and nitrite Buehler et al 2009;Roche et al 2012). It is unknown whether these reactions have any biological function.…”

“…Hp can prevent heme release from met-Hb (Fe 3þ ) and, in the presence of H 2 O 2 , attenuate the peroxidation of globin chain amino acids and the oxidative modification of external molecules (i.e., other proteins and lipids) (Miller et al 1997;Buehler et al 2009;Pimenova et al 2010). These protective functions appear to be related to the ability of Hp to firmly stabilize the structure of the bound Hb ab dimers, and to a less understood mechanism whereby Hp shields peroxidative reactions within the Hb-Hp complex from external substrates.…”

α1-Acid Glycoprotein Up-regulates CD163 via TLR4/CD14 Protein Pathway

“…Haptoglobin (Hp), 2 an acute phase plasma protein, provides the first line of defense against the effects of liberated Hb (5). When Hb binds to Hp, Hb remains sequestered within the intravascular compartment, thus attenuating Hb-mediated vasoactivity, oxidative toxicity, and tissue peroxidation (6,7). Upon complex formation, Hp transforms the Hb ␣␤-dimer into a high affinity ligand that interacts with the Hb scavenger receptor CD163, which then clears the Hb-Hp complex from the circulation (8).…”