Human peripheral blood eosinophils induce angiogenesis.
Eosinophils play a crucial role in allergic reactions and asthma. They are also involved in responses against parasites, in autoimmune and neoplastic diseases, and in fibroses. There is increasing evidence that angiogenesis plays an important role in these processes. Since eosinophils are known to produce angiogenic mediators, we have hypothesized a direct contribution of these cells to angiogenesis. The effect of human peripheral blood eosinophil sonicates on rat aortic endothelial cell proliferation (in vitro), rat aorta sprouting (ex vivo) and angiogenesis in the chick embryo chorioallantoic membrane (in vivo) have been investigated. To determine whether eosinophil-derived vascular endothelial growth factor influences the eosinophil pro-angiogenic activity, eosinophil sonicates were incubated with anti-vascular endothelial growth factor antibodies and then added to the chorioallantoic membrane. Vascular endothelial growth factor mRNA expression and vascular endothelial growth factor receptor density on the endothelial cells were also evaluated. Eosinophils were found to enhance endothelial cell proliferation and to induce a strong angiogenic response both in the aorta rings and in the chorioallantoic membrane assays. Pre-incubation of eosinophil sonicates with anti-vascular endothelial growth factor antibodies partially reduced the angiogenic response of these cells in the chorioallantoic membrane. Eosinophils also increased vascular endothelial growth factor mRNA production on endothelial cells. Eosinophils are able to induce angiogenesis and this effect is partially mediated by their pre-formed vascular endothelial growth factor. This strongly suggests an important role of eosinophils in angiogenesis-associated diseases such as asthma.
Puxeddu
Ilaria
I
Department of Pharmacology, Faculty of Medicine, School of Pharmacy, The Hebrew University of Jerusalem, POB 12065, Jerusalem 91120, Israel.
Alian
Akram
A
Piliponsky
Adrian Martin
AM
Ribatti
Domenico
D
Panet
Amos
A
Levi-Schaffer
Francesca
F
D000818:Animals; D001011:Aorta / Q000166:cytology; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D018920:Coculture Techniques; D003470:Culture Media / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D004804:Eosinophils / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013010:Sonication; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000494:pharmacology
D003470:Culture Media; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D040262:Receptors, Vascular Endothelial Growth Factor