Dose-dependent effect of radiation on angiogenic and angiostatic CXC chemokine expression in human endothelial cells.
Blood vessel growth is regulated by angiogenic and angiostatic CXC chemokines, and radiation is a vasculogenic stimulus. We investigated the effect of radiation on endothelial cell chemokine signaling, receptor expression, and migration and apoptosis. Human umbilical vein endothelial cells were exposed to a single fraction of 0, 5, or 20 Gy of ionizing radiation (IR). All vasculogenic chemokines (CXCL1-3/5-8) increased 3-13-fold after 5 or 20 Gy IR. 20 Gy induced a marked increase (1.6-4-fold) in angiostatic CXC chemokines. CXCR4 expression increased 3.5 and 7-fold at 48 h after 5 and 20 Gy, respectively. Bone marrow progenitor cell chemotaxis was augmented by conditioned media from cells treated with 5 Gy IR. Whereas 5 Gy markedly decreased intrinsic cell apoptosis (0 Gy=16%+/-3.6 vs. 5 Gy=4.5%+/-0.3), 20 Gy increased it (21.4%+/-1.2); a reflection of pro-survival angiogenic chemokine expression. Radiation induces a dose-dependent increase in pro-angiogenic CXC chemokines and CXCR4. In contrast, angiostatic chemokines and apoptosis were induced at higher (20 Gy) radiation doses. Cell migration improved significantly following 5 Gy, but not 20 Gy IR. Collectively, these data suggest that lower doses of IR induce an angiogenic cascade while higher doses produce an angiostatic profile.
The Institute of Reconstructive Plastic Surgery Laboratories, New York University School of Medicine, 560 First Avenue, TH-169, New York, NY 10016, USA.
Christopher C
CC
Chang
Oren Z
OZ
Lerman
Vishal D
VD
Thanik
Carrie L
CL
Scharf
Matthew R
MR
Greives
Robert J
RJ
Schneider
Sylvia C
SC
Formenti
Pierre B
PB
Saadeh
Stephen M
SM
Warren
Jamie P
JP
Levine
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D043165:Angiostatic Proteins / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D017209:Apoptosis / Q000528:radiation effects; D002460:Cell Line; D002465:Cell Movement / Q000528:radiation effects; D019743:Chemokines, CXC / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000276:immunology / Q000528:radiation effects*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D015151:Immunoblotting; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects
D043925:Angiogenesis Inducing Agents; D043165:Angiostatic Proteins; C527276:CXCR4 protein, human; D019743:Chemokines, CXC; D012333:RNA, Messenger; D019718:Receptors, CXCR4