Receptor reserve analysis of the human CCR3 receptor in eosinophils and CCR3-transfected cells

Umland, Shelby P.; Wan, Yuntao; Shortall, Jennifer; Shah, Himanshu; Jakway, James; Garlisi, Charles G.; Tian, Fang; Egan, Robert W.; Billah, M. Motasim

doi:10.1002/jlb.67.3.441

Cited by 22 publications

(20 citation statements)

References 33 publications

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“…Originally described by Stephenson (5) in muscarinic receptors, receptor reserve has also been observed in other systems such as G protein-coupled receptors, CCR3, and dopamine receptors (21,22). Our data demonstrate the application of receptor reserve to T cells.…”

Section: Discussionsupporting

confidence: 77%

TCR Reserve: A Novel Principle of CD4 T Cell Activation by Weak Ligands

McNeil

Evavold

2003

The Journal of Immunology

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Some ligand-receptor systems have a receptor reserve where a maximal response can be achieved by occupation of a fraction of available receptors. An implication of a receptor reserve is the expansion of the number of ligands for response. To determine whether T cells follow receptor reserve, we have characterized the effect of reducing TCR levels on CD4 T cell responses elicited by altered peptide ligands that vary in potency. Agonist peptide is unaffected by a 90% reduction in TCR level while proliferation to weak agonists is significantly inhibited when TCR expression is reduced by 40%. Thymocyte-negative selection similarly demonstrates a differential requirement of TCR for response to agonist, weak agonist, and partial agonist. Therefore, our data demonstrate receptor reserve as a novel principle of T cell activation in which excess TCRs expand the antigenic repertoire to include less potent ligands.

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Section: Discussionsupporting

confidence: 77%

TCR Reserve: A Novel Principle of CD4 T Cell Activation by Weak Ligands

McNeil

Evavold

2003

The Journal of Immunology

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“…Moreover, data presented in a recent study of CCR3 'receptor reserve' analysis might provide further explanation [41]. This study led to the conclusion that the number of receptors required to induce a response to an agonist determines the sensitivity of the assay.…”

Section: +mentioning

confidence: 81%

CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11

et al. 2003

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The chemokine receptor CXCR3 is predominantly expressed on T lymphocytes, and its agonists CXCL9, CXCL10 and CXCL11 are IFN-+ -inducible chemokines that promote Th1 responses. In contrast, the CCR3 agonists CCL11, CCL24 and CCL26 are involved in the recruitment of cells such as eosinophils and basophils during Th2 responses. Here, we report that although CCL11, CCL24 and CCL26 are neither agonists nor antagonists of CXCR3, CCL11 binds with high affinity to CXCR3. This suggests that, in vivo, CXCR3 may act as a decoy receptor, sequestering locally produced CCL11. We also demonstrate that the CXCR3 ligands inhibit CCR3-mediated functional responses of both human eosinophils and CCR3 transfectants induced by all three eotaxins, with CXCL11 being the most efficacious antagonist. The examination of CCR3-CCR1 chimeric constructs revealed that CCL11 and CXCL11 share overlapping binding sites contained within the CCR3 extracellular loops, a region that was previously shown to be essential for effective receptor-activation. Hence, eosinophil responses mediated by chemokines acting at CCR3 may be regulated by two distinct mechanisms: the antagonistic effects of CXCR3 ligands and the sequestration of CCL11 by CXCR3-expressing cells. Such interplay may serve to finely tune inflammatory responses in vivo.

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“…There are evidences that the number of eosinophils can be increased by chemoattractants such as eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein (MCP)-3 and -4 through the CC chemokine receptor 3 (CCR3) in allergic patients (Umland et al, 2000). In our study, CMR treatment significantly inhibited airway eosinophil infiltration in BALF and lung at 200 mg/kg, while eosinophils were abundant in BALF of OVA-treated mice, indicating the specific role of eosinophil in asthma process.…”

Section: Discussionmentioning

confidence: 99%