β-趋化因子CCL15影响造血祖细胞的黏附和迁移。

Beta-Chemokine CCL15 Affects the Adhesion and Migration of Hematopoietic Progenitor Cells.

作者信息

Richter Rudolf, Rüster Brigitte, Bistrian Roxana, Forssmann Wolf-Georg, Seifried Erhard, Henschler Reinhard

机构信息

Institute of Transfusion Medicine and Immune Hematology, German Red Cross Blood Donor Center, Johann Wolfgang Goethe-University Frankfurt/M., Germany ; Clinic of Immunology and Rheumatology, Hannover Medical School, Hanover, Germany.

Institute of Transfusion Medicine and Immune Hematology, German Red Cross Blood Donor Center, Johann Wolfgang Goethe-University Frankfurt/M., Germany.

出版信息

Transfus Med Hemother. 2015 Jan;42(1):29-37. doi: 10.1159/000370168. Epub 2014 Dec 19.

DOI:10.1159/000370168

PMID:25960713

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4404931/

Abstract

BACKGROUND

Hematopoietic stem and progenitor cell (HPC) motility is essential for HPC transplantation. The chemokine CXCL12 is key for HPC motility. Further regulators are of interest to improve HPC transplantation and regenerative medicine. Here the impact of the human chemokine CCL15 on HPC motility was investigated.

METHODS

CCL15 plasma concentrations were determined during HPC mobilization in humans. Activity of CCL15 on HPCs was investigated in murine assays, including chemotaxis, adhesion, and CFU-A assays, and competitive repopulation assays.

RESULTS

During HPC mobilization with granulocyte colony-stimulating factor, blood plasma contains increased concentrations (1.1 ± 0.1 ng/ml) of activated CCL15(27-92) versus 0.4 ± 0.1 ng/ml in controls (p = 0.02). CCL15(27-92) significantly enhanced CXCL12-induced transwell migration of Lin-/Sca1+ HPCs and strengthened shear stress-dependent adhesion to vascular cell adhesion molecule-1 (VCAM-1). CCL15(27-92) dose-dependently reduced the colony size in CFU-A assays performed with murine bone marrow and Lin-/Sca1+ HPCs. CCL15(27-92) did not show a direct impact on cell cycle status of HPCs. In murine repopulation assays, pretreatment of bone marrow with CCL15(27-92) significantly increased competitive repopulation.

CONCLUSION

Our results point to a regulation of HPCs by CCL15 by modulating migratory and adhesive properties of HPCs with the potency to improve HPC short-term engraftment in stem cell transplantation.

摘要

背景

造血干细胞和祖细胞（HPC）的迁移能力对于HPC移植至关重要。趋化因子CXCL12是HPC迁移的关键因素。进一步探索调控因子对于改善HPC移植和再生医学具有重要意义。本文研究了人趋化因子CCL15对HPC迁移能力的影响。

方法

测定人类HPC动员过程中CCL15的血浆浓度。通过小鼠实验研究CCL15对HPC的作用，包括趋化性、黏附性和CFU-A实验以及竞争性再增殖实验。

结果

在使用粒细胞集落刺激因子进行HPC动员期间，血浆中活化的CCL15（27-92）浓度增加（1.1±0.1 ng/ml），而对照组为0.4±0.1 ng/ml（p = 0.02）。CCL15（27-92）显著增强了CXCL12诱导的Lin-/Sca1+HPC的Transwell迁移，并增强了剪切应力依赖性对血管细胞黏附分子-1（VCAM-1）的黏附。在使用小鼠骨髓和Lin-/Sca1+HPC进行的CFU-A实验中，CCL15（27-92）剂量依赖性地减小了集落大小。CCL15（27-92）对HPC的细胞周期状态没有直接影响。在小鼠再增殖实验中，用CCL15（27-92）预处理骨髓显著增加了竞争性再增殖。