Differential activity of pro-angiogenic CXC chemokines.
We showed previously in a mouse model of lung ischemia-induced angiogenesis, enhanced expression of the three ELR+ CXC chemokines (KC, LIX, and MIP-2) and that blockade of the ligand receptor CXCR(2) limited neovascularization. The present study was undertaken to determine the relative abundance and angiogenic potential of the three CXC chemokines and whether RhoA activation explained the measured differences in potencies. We found that LIX showed the greatest absolute amount in the in vivo model 4 h after left pulmonary artery obstruction (LIX>KC>MIP-2; p<0.05). In vitro, LIX induced the greatest degree of arterial endothelial cell chemotaxis and KC was without effect. A significant increase (approximately 40%) in active RhoA was observed with both LIX and MIP-2 compared with vehicle control (p<0.05). On average, LIX induced the greatest amount of tube formation within pleural tissue in culture. Thus, the results of the present study suggest that among the three ELR+ CXC chemokines, LIX predominates in eliciting a pro-angiogenic phenotype.
Department of Medicine, Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Baltimore, MD 21224, USA.
Aigul
A
Moldobaeva
Amy
A
Baek
Lindsey
L
Eldridge
Elizabeth M
EM
Wagner
D042501:Angiogenic Proteins / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D054360:Chemokine CXCL1 / Q000378:metabolism / Q000494:pharmacology; D054426:Chemokine CXCL2 / Q000378:metabolism / Q000494:pharmacology; D054365:Chemokine CXCL5 / Q000378:metabolism / Q000494:pharmacology; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism; D008026:Ligation; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D011651:Pulmonary Artery / Q000601:surgery; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000276:immunology; D046509:Tissue Culture Techniques; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
D042501:Angiogenic Proteins; D000906:Antibodies; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; C094739:Cxcl5 protein, mouse; D004791:Enzyme Inhibitors; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; C526380:RhoA protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein