Interleukin-8 and tumor necrosis factor-alpha are involved in human aortic endothelial cell migration. The possible role of these cytokines in human aortic aneurysmal blood vessel growth.
Angiogenesis, the growth and proliferation of blood vessels, may be important in the pathogenesis of atherosclerosis and thus in human atherosclerotic abdominal aortic aneurysms (AAAs). Endothelial migration or chemotaxis is a vital component of the angiogenic response. Here, human aortic endothelial cells (hAECs) were used to investigate the effect of AAA tissue supernatants on hAEC chemotaxis. AAA tissue conditioned media were found to be chemotactic for hAECs. We have previously shown that the angiogenic cytokines interleukin (IL)-8, and tumor necrosis factor (TNF)-alpha are present in AAAs and normal aortic explant conditioned media. Currently, we have found that basic fibroblast growth factor (bFGF) and platelet-derived growth factor can also be detected in these supernatants. In order to identify whether some of these soluble mediators contributed to the chemotactic activity of these supernatants, conditioned media were preincubated with either neutralizing anti-IL-8, anti-TNF-alpha, anti-bFGF antibodies or control serum. Anti-IL-8 and anti-TNF-alpha significantly inhibited AAA tissue supernatant-induced hAEC chemotaxis (p < 0.05), while anti-bFGF did not (p not significant). These results indicate that IL-8 and TNF-alpha may be important in chemotactic activity for hAECs in vitro and possibly in AAA neovascularization. The abrogation of angiogenesis using neutralizing antibodies may be a future goal in the therapy of certain disease states such as AAA where angiogenesis plays an important role.
Szekanecz
Z
Z
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Shah
M R
MR
Harlow
L A
LA
Pearce
W H
WH
Koch
A E
AE
D000911:Antibodies, Monoclonal; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D016209:Interleukin-8; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2