Haematopoietic stem cell recruitment to injured murine liver sinusoids depends on α4β1 integrin/VCAM-1 interactions

被引：28

作者：

Kavanagh, D. P. J. ^{[1
]}

Durant, L. E. ^{[1
]}

Crosby, H. A. ^{[1
]}

Lalor, P. F. ^{[1
]}

Frampton, J. ^{[1
]}

Adams, D. H. ^{[1
]}

Kalia, N. ^{[1
]}

机构：

[1] Univ Birmingham, Sch Med, Inst Biomed Res, Ctr Cardiovasc Sci, Birmingham B15 2TT, W Midlands, England

来源：

GUT | 2010年 / 59卷 / 01期

基金：

英国医学研究理事会;

关键词：

BONE-MARROW; ADHESION MOLECULE-1; RECIRCULATING LYMPHOCYTES; REPERFUSION INJURY; PERIPHERAL-BLOOD; HEPATOCYTES; TRAFFICKING; ISCHEMIA; PECAM-1; SDF-1;

D O I：

10.1136/gut.2008.168054

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Objective: Evidence suggests haematopoietic stem cells (HSCs) can migrate to injured liver and influence tissue repair. However, mechanisms governing HSC recruitment to injured hepatic microcirculation are poorly understood. These were investigated in vivo following hepatic ischaemia-reperfusion (IR) injury and in vitro using flow-based adhesion assays. Design: Partial IR was induced in anaesthetised WT or PECAM-1(-/)-mice for 90 min. Recruitment of systemically administered HSCs was monitored and effects of function blocking antibodies against alpha(4)beta(1) integrin, CD18, CD44, PECAM-1 or VCAM-1 investigated. The kinetics and molecular events governing adhesion to murine cardiac endothelial cells in vitro were also determined. Effects of conditioned media from IR injured liver on HSC adhesion molecule expression was determined by FACS. Results: Administered HSCs homed predominantly to lungs rather than liver, highlighting a potential therapeutic hurdle. Hepatic HSC recruitment following IR injury was inhibited by anti-alpha(4)beta(1) and anti-VCAM-1 antibodies. A role for a4b1 was also confirmed using flow-based adhesion assays. Incubating HSCs with conditioned media from IR injured liver increased alpha(4)beta(1) expression. CD18, CD44 and PECAM-1 were not involved in recruitment. Conclusions: This novel study demonstrates that the alpha(4)beta(1)/VCAM-1 pathway mediates HSC recruitment to injured liver. Manipulating this pathway may enhance delivery of HSCs to the liver.

引用

页码：79 / 87

页数：9

共 48 条

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