Donor to donor variation of the chemokine receptor CCR1 on human eosinophils and its prolonged internalization by RANTES - 25/08/11
Abstract |
Rationale |
Whereas recent studies underlies the fundamental importance of the CC chemokine receptor CCR3 for the recruitment of eosinophils in allergic diseases controversial data about the expression of CCR1 on eosinophils exist. Therefore, the purpose of this study was to investigate the expression and regulation of CCR1 on eosinophils.
Methods |
Flow cytometric analysis of whole blood eosinophils or CD16-negative selected freshly isolated eosinophils from atopic and non-atopic donors using an anti-CCR1 mAb.
Results |
We found that 32% of the donors (n=24) were positive and 68% (n=49) were negative to express CCR1. Pre-incubation of isolated CCR1-positive eosinophils for 24 h with IL-3 (p=0.021), RANTES (p<0.001), MCP-3 (p=0.004), MCP-4 (p=0.006) and MIP-1⍺ (p=0.005) induced a significant down-regulation of CCR1 when compared to medium-incubated eosinophils. Internalization experiments using CCR1-positive donors revealed that RANTES (2 min: p=0.003; 60 min: p=0.038) is more effective to induce CCR1 internalization than MIP-1⍺. Whereas CCR1 re-expression after stimulation with MIP-1⍺ reached pre-stimulation levels, RANTES showed a prolonged CCR1 internalization (120 min: p<0.001; 24 h: p=0.01).
Conclusions |
A subpopulation of human donors are able to express CCR1 on the surface of eosinophils which helps to explain the different response of eosinophils to MIP-1⍺ in previous studies. It is tempting to speculate whether the higher positive charge of RANTES in comparison to its overall negative charge of MIP-1⍺ is responsible for the prolonged CCR1 internalization in response to RANTES.
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Vol 113 - N° 2S
P. S167 - février 2004 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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