PF-4/CXCL4 蛋白, Mouse (HEK293, Fc)

PF-4/CXCL4 is a member of the CXC chemokine family that is released from the alpha-granules of activated platelets. PF-4/CXCL4 binds with high affinity to heparin, with antiheparin, antiangiogenic and immunomodulatory activities. PF-4/CXCL4 plays a role in hematopoiesis and immune cell modulation^[1][2]. PF-4/CXCL4 Protein, Mouse (HEK293, Fc) is produced in HEK293 cells with a C-Terminal Fc-tag. It consists of 76 amino acids (V30-S105).

CXCL4，也称为 PF-4（血小板因子 4），是巨核细胞谱系细胞产生的 CXC 趋化因子家族的成员。在巨核细胞中，CXCL4 被合成，封装在囊泡中，并转移到 α 颗粒中，并在血小板激活后从该颗粒中分泌出来。CXCL4 也在小胶质细胞、单核细胞和活化 T 细胞中表达^[1][2]。
成熟人类 CXCL4 与以下细胞有 70% 的氨基酸序列同一性小鼠和大鼠 CXCL4。
CXCL4 储存在血小板的分泌颗粒中，并响应蛋白激酶 C 和 Rac1 激活而释放。血小板被认为是 CXCL4 的主要细胞来源。在血小板的 α 颗粒中，CXCL4 以四聚体形式与两个硫酸软骨素分子结合。CXCL4 在其氨基末端不具有 ELR 酸序列，因此不与 CXCR1 或 CXCR2 结合。CXCL4 调节肝素样分子对血管内皮细胞表面的作用，从而抑制局部抗凝血酶 III 活性，从而发挥 CXCL4 的促凝血作用。CXCL4 在体外和体内表现出抗血管生成特性，并通过多种机制抑制肿瘤新生血管形成。首先，CXCL4能够直接与血管生成生长因子（例如FGF和VEGF）相互作用，并抑制它们与细胞表面受体的相互作用。其次，CXCL4 可能结合蛋白聚糖并干扰蛋白聚糖旁观者对生长因子活性的影响。此外，最近鉴定出一种由人内皮细胞 (EC) 以细胞周期依赖性方式表达并介导 CXCL4 的抗血管生成作用的细胞表面受体，并将其命名为 CXCR3-B。CXCL4 已被证明可以调节免疫细胞的增殖、表型和功能。例如，据报道 CXCL4 可以促进单核细胞存活和巨噬细胞活化。CXCL4 诱导活化 T 淋巴细胞迁移^[1][2][3]。
CXCL4 显示出多效性生物学功能。首先，CXCL4 激活血小板、调节血小板聚集并刺激 α 颗粒蛋白的释放。CXCL4 在肝素诱导的血小板减少症 (HIT) 中发挥作用。其次，CXCL4抑制内皮细胞增殖和迁移，从而抑制血管生成。第三，CXCL4 表达免疫调节活性，例如下调 1 型 T 辅助细胞 (Th1) 细胞产生的 IFN-α，上调 2 型 T 辅助细胞中的 IL-4、IL-5 和 IL-13。Th2) 细胞。第四，CXCL4影响造血，抑制巨核细胞生成和定向红系和粒细胞-巨噬细胞集落以及原始CD34⁺祖细胞的增殖。此外，CXCL4 在系统性硬化症的浆细胞样树突状细胞 (pDC) 和严重创伤后的树突状细胞 (DC) 中也高度上调^[1][2][3]。

Recombinant mouse CXCL4 protein (2.5, 5, 25, or 50 µg/kg/day) to myocardial infarction (MI) mice at 24 h post-MI by osmotic mini-pump. CXCL4 infusion dramatically reduces 7 day post-MI survival. CXCL4 infusion also increases Ccr4 and Itgb4 and decreased Adamts8 gene levels in the infarct region^[4].

Recombinant mouse CXCL4 (5 μg/mL; for 4 h) elicites macrophages to express pro-inflammatory cytokines in peritoneal macrophages. CXCL4 significantly up-regulates the expression of Ccl3, Ccl5, Il1β, and Il6^[4].
Recombinant mouse CXCL4 (20-2000 ng/mL; for 24 h) leads to dose-dependent increase in proliferation in stellate cells. CXCL4 also induces the directed migration of stellate cells in a modified Boyden chamber. Incubation of stellate cells with Cxcl4 for 24 hours leads to increased expression of Ccl5 mRNA and Ccl5 protein^[5].

Mouse

HEK293

C-hFc

Q9Z126 (V30-S105)

56744  [NCBI]

VTSAGPEESDGDLSCVCVKTISSGIHLKHITSLEVIKAGRHCAVPQLIATLKNGRKICLDRQAPLYKKVIKKILES

40-50 kDa

Greater than 95% as determined by Tris-Bis PAGE.

无菌粉末

Lyophilized from 0.22 μm filtered solution in PBS, 200mM L-Arginine (pH 7.4). Normally 8% trehalose is added as protectant before lyophilization.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Lasagni L, et al. PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion. Blood. 2007 May 15;109(10):4127-34.  [Content Brief]

  [2]. Pieter Ruytinx, et al. CXCL4 and CXCL4L1 in cancer. Cytokine. 2018 Sep;109:65-71.  [Content Brief]

  [3]. Gabriele Domschke, et al. CXCL4-induced macrophages in human atherosclerosis. Cytokine. 2019 Oct;122:154141.  [Content Brief]

  [4]. Merry L Lindsey, et al. Exogenous CXCL4 infusion inhibits macrophage phagocytosis by limiting CD36 signalling to enhance post-myocardial infarction cardiac dilation and mortality.Cardiovasc Res. 2019 Feb 1;115(2):395-408.  [Content Brief]

  [5]. Mirko Moreno Zaldivar, et al. CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis. Hepatology. 2010 Apr;51(4):1345-53.  [Content Brief]