High level expression, activation, and antagonism of CC chemokine receptors CCR2 and CCR3 in Chinese hamster ovary cells.

Abstract:

:The specificity of leukocyte trafficking in inflammation is controlled by the interactions of chemokines with chemokine receptors. Reliable structure-function studies of chemokine-receptor interactions would benefit from cell lines that express consistent high levels of chemokine receptors. We describe herein two new Chinese hamster ovary (CHO) cell lines in which the genes for chemokine receptors CCR2 and CCR3 have been incorporated into identical positions in the host genome. CCR2 is the primary receptor for the chemokine monocyte chemoattractant protein-1 (MCP-1) whereas CCR3 is the primary receptor for the chemokines eotaxin-1, eotaxin-2 and eotaxin-3. Both receptors are expressed at >5,000,000 copies per cell, substantially higher levels than in previous cell lines, and both are competent for binding and activation by the cognate chemokines for these receptors. Using these cell lines we confirm that eotaxin-1 and eotaxin-3 can act as an agonist and an antagonist, respectively, of CCR2. In addition, we show that eotaxin-2 is an antagonist of CCR2 and MCP-1 is an agonist of CCR3. Comparison of the chemokine sequences reveals several positions that are identical in MCP-1 and eotaxin-1 but different in eotaxin-2 and eotaxin-3, suggesting that these amino acids play a role in CCR2 activation.

journal_name

Cytokine

journal_title

Cytokine

authors

Parody TR,Stone MJ

doi

10.1016/j.cyto.2004.03.013

keywords:

subject

Has Abstract

pub_date

2004-07-07 00:00:00

pages

38-46

issue

1

eissn

1043-4666

issn

1096-0023

pii

S1043466604000985

journal_volume

27

pub_type

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