M Juremalm1, N Olsson, G Nilsson. 1. Research Group on Mast Cell Biology, Department of Genetics and Pathology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Abstract
BACKGROUND: Mast cells (MCs) accumulate at sites of allergic mucosal inflammation where they act as central effectors and regulatory cells. Chemokines are believed to be crucial for the recruitment of MCs to sites of inflammation. We recently reported that human umbilical cord blood MCs (CBMCs) expresses the CC chemokine receptors, CCR1 and CCR4. We found a unique response profile to ligands of the respective receptors in which, of all tested ligands, only CCL5/RANTES-induced migration. OBJECTIVE: To further investigate the function of CCR4 in MCs. METHODS: CBMCs were used for competition binding experiments, migration, and intracellular calcium mobilization and release response studies. RESULTS: The natural ligands for CCR4, CCL17/TARC and CCL22/MDC could both compete for binding with radiolabelled CCL5. Further, both CCL17 and CCL22 act as CCR4 antagonists by inhibiting CCL5-induced migration. Although both CCL17 and CCL22 caused mobilization of intracellular calcium, none of them induced migration or histamine release. CONCLUSIONS: These results suggest that CCL5-induced migration of MCs via CCR4 can be regulated by the natural agonists CCL17 and CCL22, which are up-regulated at sites of allergic inflammation.
BACKGROUND: Mast cells (MCs) accumulate at sites of allergic mucosal inflammation where they act as central effectors and regulatory cells. Chemokines are believed to be crucial for the recruitment of MCs to sites of inflammation. We recently reported that human umbilical cord blood MCs (CBMCs) expresses the CC chemokine receptors, CCR1 and CCR4. We found a unique response profile to ligands of the respective receptors in which, of all tested ligands, only CCL5/RANTES-induced migration. OBJECTIVE: To further investigate the function of CCR4 in MCs. METHODS:CBMCs were used for competition binding experiments, migration, and intracellular calcium mobilization and release response studies. RESULTS: The natural ligands for CCR4, CCL17/TARC and CCL22/MDC could both compete for binding with radiolabelled CCL5. Further, both CCL17 and CCL22 act as CCR4 antagonists by inhibiting CCL5-induced migration. Although both CCL17 and CCL22 caused mobilization of intracellular calcium, none of them induced migration or histamine release. CONCLUSIONS: These results suggest that CCL5-induced migration of MCs via CCR4 can be regulated by the natural agonists CCL17 and CCL22, which are up-regulated at sites of allergic inflammation.
Authors: Stephen W Waldo; Yifu Li; Chiara Buono; Bin Zhao; Eric M Billings; Janet Chang; Howard S Kruth Journal: Am J Pathol Date: 2008-03-05 Impact factor: 4.307