Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein

Area of Science:

• Biochemistry
• Immunology
• Proteomics

Background:

• Haptoglobin-related protein (Hpr) is a primate-specific protein found in high-density lipoprotein (HDL) particles.
• Hpr is implicated in innate immune defense, with prior assumptions of no hemoglobin binding.
• Apolipoprotein L-I (apoL-I) is associated with Hpr in HDL particles.

Purpose of the Study:

• To investigate the hemoglobin-binding capacity of Hpr.
• To compare Hpr's interaction with hemoglobin and the scavenger receptor CD163 against haptoglobin (Hp).
• To assess the implications of Hpr-hemoglobin binding on plasma hemoglobin measurements and HDL particle function.

Main Methods:

• Recombinant Hpr was used to test direct hemoglobin binding.
• Binding assays were performed to compare Hpr and Hp affinity for hemoglobin.
• Hemoglobin-affinity precipitation was used to detect native Hpr-hemoglobin complexes in plasma HDL fractions.
• Interaction with the scavenger receptor CD163 was assessed.

Main Results:

• Recombinant Hpr demonstrated efficient binding to hemoglobin, comparable to Hp.
• Hpr did not promote high-affinity binding to the scavenger receptor CD163, unlike Hp.
• Native Hpr in plasma, associated with apoL-I in HDL, was shown to bind hemoglobin.
• Plasma contains two high-affinity hemoglobin-binding proteins: Hp and Hpr.

Conclusions:

• Plasma possesses two high-affinity hemoglobin-binding proteins: haptoglobin (Hp) and haptoglobin-related protein (Hpr).
• Only Hp-hemoglobin complexes are efficiently recognized by the scavenger receptor CD163.
• Circulating Hpr-bound hemoglobin should be considered in "free" plasma hemoglobin measurements.
• Hpr-bound hemoglobin may contribute to the biological activity of apoL-I/Hpr-containing HDL particles.