为了研究肿瘤细胞早期定植。中期生长和晚期转移等阶段以及肝脏定居巨噬细胞KF和骨髓来源巨噬细胞BMDM等巨噬细胞的功能作用。研究者使用了门静脉注射胰腺导管腺癌PDACYFP-cells模型。三个阶段，两种巨噬细胞。如何区分肝脏定居巨噬细胞KF和骨髓来源巨噬细胞BMDM？研究者在模型里面找到差异表达基因clec4f。
CLEC4F; CLECSF13; C-type (calcium dependent, carbohydrate-recognition domain) lectin, superfamily member 13; C-type lectin 13; C-type lectin domain family 4, member F; Galactose Particle Receptor; KCLR; KCR。CLEC4F/CLECSF13 蛋白是一种半乳糖和岩藻糖结合受体，表明其在内吞作用中发挥作用，表明它可能参与内化各种细胞成分并促进重要的细胞过程。
CLEC4F (C-type lectin domain; family 4, member F; also known as the Kupffer cell receptor and fucose receptor) is an 80 kDa, type II transmembrane glycoprotein member of the C-type lectin superfamily. Mature mouse CLEC4F consists of a 42 amino acid (aa) cytoplasmic domain, a 27 aa transmembrane segment, and a 479 aa extracellular domain (ECD) that contains an extended stalk region plus one carbohydrate recognition domain . Within the ECD, mouse CLEC4F shares 48% and 79% aa sequence identity with human and rat CLEC4F, respectively. The stalk region of CLEC4F is a coiled coil domain that mediates homotrimer formation. CLEC4F is expressed on Kupffer cells in the liver, but not on macrophages in other tissues. CLEC4F preferentially binds galactose and N‑acetylgalactosamine in a calcium-dependent manner. Its activity at neutral, but not at acidic pH, suggests a capacity to internalize and release ligands into the endosomal system.
如何通过流式区分：肝脏巨噬细胞和骨髓来源巨噬细胞流式区分圈门策略见下图。如下是圈门策略。
Flow Cytometry gating schema. a, Representative dot plots showing gating strategy for identifying macrophage populations in the liver. Gates were based on FMOs. Macrophages were defined as live, single cells, expressing CD45, CD11b, and F4/80 and lacking expression of CD3, CD19, CD11c, and Ly6G. Kupffer cells (KC) were distinguished from bone marrow derived macrophages (BMDM) based on Clec4f expression. Staining is representative of a liver sample from a C57BL/6 mouse. b, Representative FCM gating strategies for detection of YFP+ tumor cells in the liver after iPo injection of PDACYFP cells. Populations shown were gated on single, live cells.
Clodronate Liposomes氯膦酸盐脂质体清除肝脏巨噬细胞，疾病模型为：门静脉注射PDACYFP-cells。PDAC是胰腺导管腺癌（Pancreatic Ductal Adenocarcinoma）的缩写，属于胰腺癌中常见且恶性程度高的类型，占胰腺恶性肿瘤的85%-90%。它起源于胰腺导管上皮细胞，侵袭性强、进展迅速，多数患者确诊时已处于中晚期，5年生存率不足10%。荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：Kupffer 细胞可防止小鼠胰腺导管腺癌转移到肝脏。Clec4f可以区分肝脏巨噬细胞KF和骨髓来源巨噬细胞BMDM吗？详细类容可以见如下文献。
论文信息：
论文题目：Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice
期刊名称：Nature Communications
时间期卷：14, Article number: 6330 (2023)
在线时间：2023年10月10日
DOI：doi.org/10.1038/s41467-023-41771-z
产品信息：
货号：C-010
规格：10ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes
办事处：Target Technology(靶点科技)
