TY - JOUR
T1 - Identification of rantes receptors on human monocytic cells
T2 - Competition for binding and desensitization by homologous chemotactic cytokines
AU - Wang, Ji Ming
AU - McVicar, Daniel W.
AU - Oppenheim, Joost J.
AU - Kelvin, David J.
PY - 1993/3/1
Y1 - 1993/3/1
N2 - R.ANTES (regulated on activation, normal T expressed and secreted) is a member of the chemotactic cytokine (chemokine) β subfamily. High affinity receptors for RANTES have been identified on a human monocytic leukemia cell line THP-1, which responded to RANTES in chemotaxis and calcium mobilization assays. Steady-state binding data analyses revealed approximately 700 binding sites/cell on THP-1 cells with a Kd value of 400 pM, comparable to that expressed on human peripheral blood monocytes. The RANTES binding to monocytic cells was competed for by monocyte chemotactic and activating factor (MCAF) and macrophage inflammatory protein 1 (MIP-1) α, two other chemokine β cytokines. Although MCAF and MIP-lα competed for R.ANTES binding to monocytes with apparent lower affinity (with estimated Kd of 6 and 1.6, nM respectively) both of these cytokines effectively desensitized the calcium mobilization induced by RANTES. The chemotactic response of THP-1 cells to RANTES was also markedly inhibited by preincubation with MCAF or MIP-lα. In contrast, R.ANTES did not desensitize the THP-1 calcium mobilization and chemotaxis in response to MCAF or MIP-lα. These results, together with our previous observations that RANTES did not compete for MCAF or MIP-lα binding on monocytic cells, indicate the expression of promiscuous receptors on monocytes that recognize one or more cytokines within the chemokine β family.
AB - R.ANTES (regulated on activation, normal T expressed and secreted) is a member of the chemotactic cytokine (chemokine) β subfamily. High affinity receptors for RANTES have been identified on a human monocytic leukemia cell line THP-1, which responded to RANTES in chemotaxis and calcium mobilization assays. Steady-state binding data analyses revealed approximately 700 binding sites/cell on THP-1 cells with a Kd value of 400 pM, comparable to that expressed on human peripheral blood monocytes. The RANTES binding to monocytic cells was competed for by monocyte chemotactic and activating factor (MCAF) and macrophage inflammatory protein 1 (MIP-1) α, two other chemokine β cytokines. Although MCAF and MIP-lα competed for R.ANTES binding to monocytes with apparent lower affinity (with estimated Kd of 6 and 1.6, nM respectively) both of these cytokines effectively desensitized the calcium mobilization induced by RANTES. The chemotactic response of THP-1 cells to RANTES was also markedly inhibited by preincubation with MCAF or MIP-lα. In contrast, R.ANTES did not desensitize the THP-1 calcium mobilization and chemotaxis in response to MCAF or MIP-lα. These results, together with our previous observations that RANTES did not compete for MCAF or MIP-lα binding on monocytic cells, indicate the expression of promiscuous receptors on monocytes that recognize one or more cytokines within the chemokine β family.
UR - http://www.scopus.com/inward/record.url?scp=0027533666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027533666&partnerID=8YFLogxK
U2 - 10.1084/jem.177.3.699
DO - 10.1084/jem.177.3.699
M3 - Article
C2 - 7679707
AN - SCOPUS:0027533666
SN - 0022-1007
VL - 177
SP - 699
EP - 705
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
ER -