Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors. C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3.
Monocyte chemotactic protein-3 (MCP3) is recently identified and molecularly cloned C-C chemokine that is chemotactic for and activates a great variety of inflammatory cell types. MCP3 has been reported to interact with several C-C chemokine receptors, which can be simultaneously or selectively expressed on leukocyte subpopulations. In order to isolate receptor(s) for MCP3, a cDNA library was constructed using mRNA from a human NK-like cell line, YT. These cells showed high affinity binding sites for 125I-MCP3 and migrated in response to MCP3. A chemokine receptor cDNA clone, designated YT4, was sequenced and found to be identical to the known C-C CKR1 or macrophage inflammatory protein-1 alpha (MIP1 alpha)/Rantes receptor. YT4 cDNA was subcloned into a mammalian expression vector, and stable transfectants were prepared using the embryonic kidney cell line 293. The transfectants (YT4/293) showed high affinity binding for 125I-MCP3 in addition to specifically binding 125I-MIP1 alpha and 125I-Rantes. All three C-C chemokines were able to cross-compete for binding sites on YT4/293 cells and induced directional migration of YT4/293 cells in vitro, with MCP3 being the most potent chemoattractant. MCP3, MIP1 alpha, and Rantes were equally able to cross-attenuate the migratory response of YT4/293 cells to one another. In contrast, MCP1 and MIP1 beta had very limited capacity to compete for MCP3 binding on YT4/293 cells and had only a minor attenuating effect on MCP3-induced migration. Since MCP3 has been reported to use MCP1 receptor(s), our results with transfected 293 cells expressing only C-C CKR1 clearly establish that C-C CKR1 is also a functional receptor for MCP3.
Ben-Baruch
A
A
Laboratory of Molecular Immunoregulation, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA.
Xu
L
L
Young
P R
PR
Bengali
K
K
Oppenheim
J J
JJ
Wang
J M
JM
D001667:Binding, Competitive; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D002630:Chemotactic Factors / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D015846:Monokines / Q000378:metabolism; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction
C515450:CCL7 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D002630:Chemotactic Factors; D016207:Cytokines; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D015846:Monokines; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C080633:macrophage inflammatory protein 1alpha receptor