Abstract

Haptoglobin-related protein (Hpr) is a plasma protein with high sequence similarity to haptoglobin (Hp). Like Hp, Hpr also binds hemoglobin (Hb) with high affinity, but it does not bind to the Hb-Hp receptor CD163 on macrophages. The Hpr concentration is markedly lower than Hp in plasma and its regulation is not understood. In the present study, we have developed non-crossreactive antibodies to Hpr to analyze the Hpr concentration in 112 plasma samples from anonymized individuals and compared it to Hp. The results show that plasma Hpr correlated with Hp concentrations (rho = 0.46, p = .0001). Hpr accounts for on average 0.35% of the Hp/Hpr pool but up to 29% at low Hp levels. Furthermore, the Hpr concentrations were significantly lower in individuals with the Hp2-2 phenotype compared to those with the Hp2-1 or Hp1-1 phenotypes. Experimental binding analysis did not provide evidence that Hpr associates with Hp and in this way is removed via CD163. In conclusion, the Hpr concentration correlates to Hp concentrations and Hp-phenotypes by yet unknown mechanisms independent of CD163-mediated removal of Hb-Hp complexes.

摘要

触珠蛋白相关蛋白 (Hpr) 是与触珠蛋白 (Hp) 具有高度序列相似性的血浆蛋白。与 Hp 一样，Hpr 也以高亲和力结合血红蛋白 (Hb)，但不与巨噬细胞上的 Hb-Hp 受体 CD163 结合。Hpr 浓度明显低于血浆中的 Hp，其调节机制尚不清楚。在本研究中，我们开发了针对 Hpr 的非交叉反应性抗体，以分析来自匿名个体的 112 个血浆样本中的 Hpr 浓度，并将其与 Hp 进行比较。结果表明血浆 Hpr 与 Hp 浓度相关 (rho = 0.46, p = .0001)。Hpr 平均占 Hp/Hpr 池的 0.35%，但在低 Hp 水平时高达 29%。此外，与具有 Hp2-1 或 Hp1-1 表型的个体相比，具有 Hp2-2 表型的个体的 Hpr 浓度显着降低。实验结合分析没有提供 Hpr 与 Hp 相关的证据，并以这种方式通过 CD163 去除。总之，Hpr 浓度与 Hp 浓度和 Hp 表型相关，其机制尚不清楚，与 CD163 介导的 Hb-Hp 复合物去除无关。