為了研究腫瘤細胞早期定植。中期生長和晚期轉移等階段以及肝臟定居巨噬細胞KF和骨髓來源巨噬細胞BMDM等巨噬細胞的功能作用。研究者使用了門靜脈注射胰腺導管腺癌PDACYFP-cells模型。三個階段，兩種巨噬細胞。如何區分肝臟定居巨噬細胞KF和骨髓來源巨噬細胞BMDM？研究者在模型里面找到差異表達基因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 蛋白是一種半乳糖和巖藻糖結合受體，表明其在內吞作用中發揮作用，表明它可能參與內化各種細胞成分并促進重要的細胞過程。
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.
如何通過流式區分：肝臟巨噬細胞和骨髓來源巨噬細胞流式區分圈門策略見下圖。如下是圈門策略。
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氯膦酸鹽脂質體清除肝臟巨噬細胞，疾病模型為：門靜脈注射PDACYFP-cells。PDAC是胰腺導管腺癌（Pancreatic Ductal Adenocarcinoma）的縮寫，屬于胰腺癌中常見且惡性程度高的類型，占胰腺惡性腫瘤的85%-90%。它起源于胰腺導管上皮細胞，侵襲性強、進展迅速，多數患者確診時已處于中晚期，5年生存率不足10%。荷蘭Liposoma巨噬細胞清除劑Clodronate Liposomes見刊于Nature Communications：Kupffer 細胞可防止小鼠胰腺導管腺癌轉移到肝臟。Clec4f可以區分肝臟巨噬細胞KF和骨髓來源巨噬細胞BMDM嗎？詳細類容可以見如下文獻。
論文信息：
論文題目：Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice
期刊名稱：Nature Communications
時間期卷：14, Article number: 6330 (2023)
在線時間：2023年10月10日
DOI：doi.org/10.1038/s41467-023-41771-z
產品信息：
貨號：C-010
規格：10ml
品牌：Liposoma
產地：荷蘭
名稱：Clodronate Liposomes
辦事處：Target Technology(靶點科技)
