Abstract：
:The chemokine CCL2 serves to target circulating monocytes and other leukocytes to tissue during innate immune responses, and modulates the progression of chronic inflammatory disease through activation of the receptor CCR2. Here, we show that co-activation of the P2Y₆ purinergic receptor (encoded by P2RY₆) occurs when THP-1 cells and human peripheral blood mononuclear cells sense CCL2 through CCR2. Furthermore, P2Y₆ receptor activation accounts for ∼80% of the intracellular Ca²⁺ signal evoked by CCL2. Scavenging extracellular nucleotides with apyrase caused a fourfold reduction in THP-1 sensitivity to CCL2, whereas inhibition of CD39-like ectonucleotidases potentiated CCL2-evoked Ca²⁺ responses. Pharmacological inhibition of P2Y₆ impaired CCL2-evoked Ca²⁺ signalling and chemotaxis in peripheral blood mononuclear cells and THP-1 cells. Furthermore, stable P2Y₆ receptor knockdown (of twofold) in THP-1 cells impaired CCL2-evoked Ca²⁺ signalling, chemotaxis and adhesion to TNFα-treated HUVECs. We demonstrate that THP-1 cells rapidly secrete ATP during signalling downstream of the CCL2-CCR2 axis and suggest this might act as a mechanism for P2Y₆ receptor co-activation following CCL2 activation of the CCR2 receptor. The discovery that P2Y₆ receptor mediates leukocyte responsiveness to CCL2 represents a new mechanism by which to modulate CCL2 signals.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Campwala H,Sexton DW,Crossman DC,Fountain SJdoi
10.1242/jcs.159012subject
Has Abstractpub_date
2014-11-15 00:00:00pages
4964-73issue
Pt 22eissn
0021-9533issn
1477-9137pii
jcs.159012journal_volume
127pub_type
杂志文章abstract：:Chromatin is no longer considered to be a static structural framework for packaging DNA within the nucleus but is instead believed to be an interactive component of DNA metabolism. The ordered assembly of chromatin produces a nucleoprotein template capable of epigenetically regulating the expression and maintenance of...
journal_title：Journal of cell science
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更新日期：2000-08-01 00:00:00
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abstract：:Actin cytoskeleton self-organization in two cell types, fibroblasts and epitheliocytes, was studied in cells confined to isotropic adhesive islands. In fibroblasts plated onto islands of optimal size, an initially circular actin pattern evolves into a radial pattern of actin bundles that undergo asymmetric chiral swir...
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journal_title：Journal of cell science
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doi：
更新日期：1977-01-01 00:00:00
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更新日期：2005-02-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
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更新日期：2003-10-01 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：1976-12-01 00:00:00
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更新日期：2010-07-15 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2002-12-15 00:00:00
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pub_type： 杂志文章
doi：
更新日期：1977-08-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
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doi：
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