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.
Chang
Christopher C
CC
The Institute of Reconstructive Plastic Surgery Laboratories, New York University School of Medicine, 560 First Avenue, TH-169, New York, NY 10016, USA.
Lerman
Oren Z
OZ
Thanik
Vishal D
VD
Scharf
Carrie L
CL
Greives
Matthew R
MR
Schneider
Robert J
RJ
Formenti
Sylvia C
SC
Saadeh
Pierre B
PB
Warren
Stephen M
SM
Levine
Jamie P
JP
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