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High-Mobility Group Box 1 Activates Integrin-Dependent Homing of Endothelial Progenitor Cells
- Source :
- Circulation Research. 100:204-212
- Publication Year :
- 2007
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2007.
-
Abstract
- Endothelial progenitor cells (EPCs) are recruited to ischemic regions and improve neovascularization. Integrins contribute to EPC homing. High-mobility group box 1 (HMGB1) is a nuclear protein that is released extracellularly on cell necrosis and tissue damage, eliciting a proinflammatory response and stimulating tissue repair. In the present study, we investigated the effects of HMGB1 on EPC homing. EPCs express the HMGB1 receptors RAGE (receptor for advanced glycation end products) and TLR2 (Toll-like receptor 2). EPC migration was stimulated by HMGB1 in a RAGE-dependent manner. In addition, the HMGB1-induced migration of EPCs on fibronectin and fibrinogen was significantly inhibited by antibodies against β 1 and β 2 integrins, respectively. Short-term prestimulation of EPCs with HMGB1 also increased EPC adhesion to endothelial cell monolayers, and this effect was blocked by antibodies to β 2 integrins or RAGE. HMGB1 increased EPC adhesion to the immobilized integrin ligands intercellular adhesion molecule-1 and fibronectin in a RAGE-dependent manner. Strikingly, HMGB1 rapidly increased integrin affinity and induced integrin polarization. Using intravital microscopy in a tumor model of neovascularization, prestimulation of EPCs with HMGB1 enhanced the initial in vivo adhesion of EPCs to microvessels and the recruitment of EPCs in the tumor tissue. In addition, prestimulation of EPCs with HMGB1 increased the homing of EPCs to ischemic muscles. In conclusion, these data represent a link between HMGB1 and integrin functions of EPCs and demonstrate that HMGB1 stimulates EPC homing to ischemic tissues. These results may provide a platform for the development of novel therapeutic approaches to improve EPC homing.
- Subjects :
- Integrins
Physiology
Integrin
chemical and pharmacologic phenomena
HMGB1
Proinflammatory cytokine
Neovascularization
Cell Movement
Ischemia
medicine
Animals
Humans
HMGB1 Protein
Progenitor cell
Cells, Cultured
biology
Stem Cells
Endothelial Cells
Cell biology
Endothelial stem cell
Fibronectin
embryonic structures
cardiovascular system
biology.protein
Cattle
medicine.symptom
Cardiology and Cardiovascular Medicine
circulatory and respiratory physiology
Homing (hematopoietic)
Subjects
Details
- ISSN :
- 15244571 and 00097330
- Volume :
- 100
- Database :
- OpenAIRE
- Journal :
- Circulation Research
- Accession number :
- edsair.doi.dedup.....af34caae543cb49fd383d033a1927d93