Enhancing the adhesion of hematopoietic precursor cell integrins with hydrogen peroxide increases recruitment within murine gut.
Hematopoietic stem cells (HSCs) migrate to injury sites and aid in tissue repair. However, clinical success is poor and is partially due to limited HSC recruitment. We hypothesized that HSC pretreatment with H2O2 would enhance their recruitment to injured gut. As HSCs are rare cells, the number of primary cells obtained from donors is often inadequate for functional experiments. To circumvent this, in this study we utilized a functionally relevant cell line, HPC-7. Anesthetized mice were subjected to intestinal ischemia-reperfusion (IR) injury, and HPC-7 recruitment was examined intravitally. Adhesion to endothelial cells (ECs), injured gut sections, and ICAM-1/VCAM-1 protein were also quantitated in vitro. H2O2 pretreatment significantly enhanced HPC-7 recruitment to injured gut in vivo. A concomitant reduction in pulmonary adhesion was also observed. Enhanced adhesion was also observed in all in vitro models. Increased clustering of α4 and β2 integrins, F-actin polymerization, and filopodia formation were observed in pretreated HPC-7s. Importantly, H2O2 did not reduce HPC-7 viability or proliferative ability. HPC-7 recruitment to injured gut can be modulated by H2O2 pretreatment. This may be through increasing the affinity or avidity of surface integrins that mediate HPC-7 homing to injured sites or through stimulating the migratory apparatus. Strategies that enhance hematopoietic stem/progenitor cell recruitment may ultimately affect their therapeutic efficacy.
Centre for Cardiovascular Sciences, Institute of Biomedical Research, The Medical School, University of Birmingham, Edgbaston, Birmingham, UK.
Dean P J
DP
Kavanagh
Adrian I
AI
Yemm
J Steven
JS
Alexander
Jon
J
Frampton
Neena
N
Kalia
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005629:Frozen Sections; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy
D018821:CD18 Antigens; D017077:Culture Media, Conditioned; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine