IL-8 and angiogenesis: evidence that human endothelial cells lack receptors and do not respond to IL-8 in vitro.
It has been established that IL-8 triggers angiogenesis in vivo, but this effect may be mediated either by IL-8-recruited leukocytes or by direct actions of IL-8 upon endothelial cells (EC). We have approached this question by examining interactions of recombinant human IL-8 with cultured large vessel and microvascular human EC. We are unable to detect specific IL-8 binding to cultured human umbilical vein endothelial cells (HUVEC) or leukocyte-like IL-8 receptor mRNA expression by either cultured HUVEC or human dermal microvascular endothelial cells (DMEC). We find no alteration of cytoplasmic calcium concentration ([Ca2+]i) in either cell type in response to IL-8 treatment. Finally, we find no IL-8-induced change in EC proliferative rates in the presence or absence of endothelial cell growth factor. Our data favour an indirect action for IL-8 as an angiogenic factor.
Petzelbauer
P
P
Molecular Cardiobiology Program, Yale University School of Medicine, New Haven, Connecticut 06536-0812, USA.
Watson
C A
CA
Pfau
S E
SE
Pober
J S
JS
D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000235:genetics*; D023062:Receptors, Interleukin-8A
D016209:Interleukin-8; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D002118:Calcium