Functional expression of CCR2 by human fetal astrocytes.
Astrocytes from different sources bind the chemokine monocyte chemoattractant factor (MCP-1), yet functional expression in these cells of CCR2, the major receptor for this ligand, has been a matter of controversy. Here we show that cultured human fetal astrocytes express CCR2 at the mRNA and protein levels, and display chemotaxis and calcium flux in response to MCP-1. Surface CCR2 protein expression and MCP-1 binding activity were observed to undergo near parallel downmodulation and recovery following MCP-1 exposure, supporting the argument that CCR2, and not another receptor, mediates MCP-1 ligation in these cells. Downmodulation was further determined to occur via receptor internalization, and to apparently proceed via both clathrin-coated vesicles and caveolae, the latter being a novel mode for the endocytosis of chemokine receptors. Insofar as MCP-1 is thought to mediate inflammatory and developmental processes within the central nervous system (CNS), such astrocyte responses to this chemokine are likely to significantly impact physiological and pathophysiological events at the blood-brain barrier and within the CNS parenchyma.
Andjelkovic
Anuska V
AV
Blood-Brain Barrier Laboratory, Department of Pharmacology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Song
Li
L
Dzenko
Kirk A
KA
Cong
Hui
H
Pachter
Joel S
JS
D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000196:embryology*; D002118:Calcium / Q000378:metabolism; D022461:Caveolins / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000493:pharmacokinetics / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C515334:CCR2 protein, human; D022461:Caveolins; D018932:Chemokine CCL2; D007375:Interleukin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C106354:flotillins; D002118:Calcium