Scholarlink

<p>Mild rupture of aged erythrocytes occurs in the spleen, resulting in hemoglobin (Hb) release, whereas pathological hemolysis characterizes several diseases. Hb detoxification is attributed to macrophages, but other routes of Hb clearance remain elusive. Here, we uncover that Hb uptake is chiefly executed by liver sinusoidal endothelial cells (LSECs) via macropinocytosis. Consistently, LSECs display proteomic signatures indicative of heme catabolism, ferritin iron storage, antioxidant defense, and macropinocytic capacity, alongside high iron content and expression of the iron exporter ferroportin. Erythrocyte/Hb transfusion assays demonstrate that splenic macrophages excel in erythrophagocytosis, while LSECs and Kupffer cells scavenge the spleen-borne hemolysis products Hb and erythrocyte membranes, respectively. High Hb doses result in transient hepatic iron retention, LSEC-specific induction of heme-catabolizing <i>Hmox1</i>, along with the iron-sensing <i>Bmp6</i>-hepcidin axis culminating in hypoferremia. Transcriptional induction of <i>Bmp6</i> in LSECs is phenocopied by erythrocyte lysis upon phenylhydrazine and elicits a distinct transcriptional signature compared to iron. Collectively, we identify LSECs as key Hb scavengers, a function that establishes the spleen-to-liver axis for iron recycling and contributes to heme detoxification during hemolysis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月6日

查看全文
  • Gabriela Zurawska,
  • Zuzanna Sas,
  • Aneta Jończy,
  • Raghunandan Mahadeva,
  • Patryk Slusarczyk,
  • Marta Chwałek,
  • Daniel Seehofer,
  • Georg Damm,
  • Rafał Mazgaj,
  • Marcin Skórzyński,
  • Maria Kulecka,
  • Izabela Rumieńczyk,
  • Morgane Moulin,
  • Kamil Jastrzębski,
  • Kevin Waldron,
  • Michal Mikula,
  • Anders Etzerodt,
  • Remigiusz Serwa,
  • Marta Miączyńska,
  • Tomasz P Rygiel,
  • Katarzyna Mleczko-Sanecka

摘要

Mild rupture of aged erythrocytes occurs in the spleen, resulting in hemoglobin (Hb) release, whereas pathological hemolysis characterizes several diseases. Hb detoxification is attributed to macrophages, but other routes of Hb clearance remain elusive. Here, we uncover that Hb uptake is chiefly executed by liver sinusoidal endothelial cells (LSECs) via macropinocytosis. Consistently, LSECs display proteomic signatures indicative of heme catabolism, ferritin iron storage, antioxidant defense, and macropinocytic capacity, alongside high iron content and expression of the iron exporter ferroportin. Erythrocyte/Hb transfusion assays demonstrate that splenic macrophages excel in erythrophagocytosis, while LSECs and Kupffer cells scavenge the spleen-borne hemolysis products Hb and erythrocyte membranes, respectively. High Hb doses result in transient hepatic iron retention, LSEC-specific induction of heme-catabolizing Hmox1, along with the iron-sensing Bmp6-hepcidin axis culminating in hypoferremia. Transcriptional induction of Bmp6 in LSECs is phenocopied by erythrocyte lysis upon phenylhydrazine and elicits a distinct transcriptional signature compared to iron. Collectively, we identify LSECs as key Hb scavengers, a function that establishes the spleen-to-liver axis for iron recycling and contributes to heme detoxification during hemolysis.