CCL2 binding is CCR2 independent in primary adult human astrocytes.
Chemokines are low relative molecular mass proteins, which have chemoattractant actions on many cell types. The chemokine, CCL2, has been shown to play a major role in the recruitment of monocytes in central nervous system (CNS) lesions in multiple sclerosis (MS). Since resident astrocytes constitute a major source of chemokine synthesis including CCL2, we were interested to assess the regulation of CCL2 by astrocytes. We showed that CCL2 bound to the cell surface of astrocytes and binding was not modulated by inflammatory conditions. However, CCR2 protein was not detected nor was activation of the classical CCR2 downstream signaling pathways. Recent studies have shown that non-signaling decoy chemokine receptors bind and modulate the expression of chemokines at site of inflammation. Here, we show that the D6 chemokine decoy receptor is constitutively expressed by primary human adult astrocytes at both mRNA and protein level. In addition, CCL3, which binds to D6, but not CCL19, which does not bind to D6, displaced CCL2 binding to astrocytes; indicating that CCL2 may bind to this cell type via the D6 receptor. Our results suggest that CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the D6 decoy chemokine receptor. Therefore we propose that astrocytes are implicated in both the establishment of chemokine gradients for the migration of leukocytes into and within the CNS and in the regulation of CCL2 levels at inflammatory sites in the CNS.
Biomedical Research Centre, Faculty of Health and Wellbeing, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK. Antoine.Fouillet@ens-lyon.fr
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Fouillet
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Mawson
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Suliman
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Sharrack
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Romero
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Woodroofe
D000328:Adult; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D054447:Receptors, CCR10 / Q000378:metabolism / Q000502:physiology; D054390:Receptors, CCR2 / Q000378:metabolism*; D000097628:Chemokine Receptor D6
D018932:Chemokine CCL2; D018836:Inflammation Mediators; D054447:Receptors, CCR10; D054390:Receptors, CCR2; D000097628:Chemokine Receptor D6; C111835:CCL2 protein, human; C515334:CCR2 protein, human