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Duffy antigen receptor for chemokines mediates chemokine endocytosis through a macropinocytosis-like process in endothelial cells

Zhao, Y and Mangalmurti, NS and Xiong, Z and Prakash, B and Guo, F and Stolz, DB and Lee, JS (2011) Duffy antigen receptor for chemokines mediates chemokine endocytosis through a macropinocytosis-like process in endothelial cells. PLoS ONE, 6 (12).

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Background: The Duffy antigen receptor for chemokines (DARC) shows high affinity binding to multiple inflammatory CC and CXC chemokines and is expressed by erythrocytes and endothelial cells. Recent evidence suggests that endothelial DARC facilitates chemokine transcytosis to promote neutrophil recruitment. However, the mechanism of chemokine endocytosis by DARC remains unclear. Methodology/Principal Findings: We investigated the role of several endocytic pathways in DARC-mediated ligand internalization. Here we report that, although DARC co-localizes with caveolin-1 in endothelial cells, caveolin-1 is dispensable for DARC-mediated 125I-CXCL1 endocytosis as knockdown of caveolin-1 failed to inhibit ligand internalization. 125I-CXCL1 endocytosis by DARC was also independent of clathrin and flotillin-1 but required cholesterol and was, in part, inhibited by silencing Dynamin II expression. 125I-CXCL1 endocytosis was inhibited by amiloride, cytochalasin D, and the PKC inhibitor Gö6976 whereas Platelet Derived Growth Factor (PDGF) enhanced ligand internalization through DARC. The majority of DARC-ligand interactions occurred on the endothelial surface, with DARC identified along plasma membrane extensions with the appearance of ruffles, supporting the concept that DARC provides a high affinity scaffolding function for surface retention of chemokines on endothelial cells. Conclusions/Significance: These results show DARC-mediated chemokine endocytosis occurs through a macropinocytosis-like process in endothelial cells and caveolin-1 is dispensable for CXCL1 internalization. © 2011 Zhao et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Zhao, Y
Mangalmurti, NS
Xiong, Zzex1@pitt.eduZEX1
Prakash, B
Guo, F
Stolz, DBdonna.stolz@pitt.eduDSTOLZ
Lee, JSjsl26@pitt.eduJSL26
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Center for Biologic Imaging
Date: 27 December 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0029624
Schools and Programs: School of Medicine > Cell Biology and Molecular Physiology
School of Medicine > Critical Care Medicine
Refereed: Yes
MeSH Headings: Amiloride--pharmacology; Chemokines--metabolism; Duffy Blood-Group System--immunology; Endocytosis; Endothelium--cytology; Endothelium--metabolism; Flow Cytometry; Humans; Microscopy, Electron, Transmission; Pinocytosis; Protein Kinase C--metabolism; Receptors, Antigen--immunology; Receptors, Antigen--metabolism
Other ID: NLM PMC3246497
PubMed Central ID: PMC3246497
PubMed ID: 22216333
Date Deposited: 07 Sep 2012 19:18
Last Modified: 22 Jun 2021 14:55


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