Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and T(H)1-like/CD45RO(+) T cells

Chemokines and their receptors control the emigration of leukocytes during inflammation. The role of the RANTES (regulated on activation normal T-cell expressed and secreted) receptors CCR1 and CCR5 in the selective recruitme nt of monocytes, T(H)1-like T-cell clones, and peripheral T cells enriched for CD45RO(+) "memory" cells were tested in a system in which arrest under flow conditions is triggered by RANTES immobilized to activated endothelium . With the use of selective nonpeptide receptor antagonists or blocking ant ibodies, it was found that the RANTER-induced arrest of these cells was med iated predominantly by CCR1. In contrast, CCR5 mainly contributed to the sp reading in shear flow, and both CCR1 and CCR5 supported transendothelial ch emotaxis toward RANTES, The data in this study reveal specialized roles of apparently redundant receptors in distinct steps of leukocyte trafficking a nd suggest that not all receptors currently used to define mononuclear cell subsets are involved in their direct recruitment from the circulation.