Expression of CCR2 by endothelial cells : implications for MCP-1 mediated wound injury repair and In vivo inflammatory activation of endothelium.
Endothelial cell proliferation and migration may play a central role in angiogenesis, wound healing, and atherosclerosis. Although CXC chemokines can act on endothelial cells by influencing proliferation, an involvement of CC chemokines and endothelial expression of chemokine receptors remains to be elucidated. Reverse transcription-polymerase chain reaction, RNase protection, Western blot, and flow cytometric analysis showed that human umbilical vein endothelial cells express mRNA and surface protein of the monocyte chemotactic protein-1 (MCP-1) receptor CCR2, which was upregulated by inflammatory cytokines. MCP-1 induced migration of endothelial cells in a transwell assay, which was inhibited by the 9-76 MCP-1 receptor antagonist. Increased secretion of MCP-1 or interleukin-8, but not RANTES, on endothelial injury suggested a functional role of CCR2 in wound repair as measured by ELISA. After mechanical injury to endothelial monolayers, which spontaneously closed within 24 hours, wound repair was delayed by the 9-76 antagonist and by a blocking monoclonal antibody to MCP-1, but not to interleukin-8, and was improved by exogenous MCP-1. This was confirmed by quantification of cell migration into the wound area, whereas proliferation and viability were unaltered by MCP-1 or its analogue. Notably, immunohistochemistry of inflamed tissue revealed CCR2 staining on arterial, venous, and venular endothelium affected by cellular infiltration. This is the first demonstration of endothelial CCR2 expression ex vivo, inferring its involvement in inflammatory conditions. Thus endothelial cells express functional CCR2 that may have important implications for endothelial wound repair and inflammatory reactions.
Weber
K S
KS
Institut für Prophylaxe der Kreislaufkrankheiten, München, Germany. kim.weber@klp.med.uni-muenchen.de
Nelson
P J
PJ
Gröne
H J
HJ
Weber
C
C
D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000293:injuries / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D014657:Vasculitis / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000503:physiopathology
C515334:CCR2 protein, human; D018932:Chemokine CCL2; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine