Combadiere C, Ahuja S K, Van Damme J, Tiffany H L, Gao J L, Murphy P M
Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 1995 Dec 15;270(50):29671-5. doi: 10.1074/jbc.270.50.29671.
The CC chemokine monocyte chemoattractant protein-3 (MCP-3) activates human monocytes, lymphocytes, basophils, and eosinophils. MCP-3 has been reported to induce [Ca2+]i changes in cells transfected with the monocyte-selective MCP-1 receptor 2B (CC CKR2B) and competes for 125I-MCP-1 binding on CC CKR2B, suggesting that it may mediate monocyte responses to MCP-3. However, we now show that MCP-3 is a ligand and potent agonist for the macrophage inflammatory protein-1 alpha (MIP-1 alpha)/regulated on activation, normal T expressed, and secreted protein (RANTES) receptor CC CKR1 (rank order for [Ca2+]i changes = MIP-1 alpha > MCP-3 > RANTES), which is expressed in monocytes > neutrophils > eosinophils. 125I-MCP-3 bound directly to CC CKR1 and CC CKR2B (Ki = 8 and 7 nM, respectively). Binding to CC CKR1 was competed by all CC chemokines tested except MCP-1. In contrast, binding to CC CKR2B was competed only by MCP-3 and MCP-1. Both MCP-1 and MCP-3 were equipotent agonists (EC50 = 10 nM for [Ca2+]i changes). Thus, MCP-3 is a functional ligand for both CC CKR1 and CC CKR2B, which otherwise have distinct selectivities for CC chemokines. These data suggest that monocyte responses to MCP-3 could be mediated by both CC CKR2B and CC CKR1, whereas eosinophil responses to MCP-3 could be mediated by CC CKR1.
C-C趋化因子单核细胞趋化蛋白-3（MCP-3）可激活人单核细胞、淋巴细胞、嗜碱性粒细胞和嗜酸性粒细胞。据报道，MCP-3可诱导转染了单核细胞选择性MCP-1受体2B（CC CKR2B）的细胞内[Ca2+]i变化，并能竞争CC CKR2B上125I-MCP-1的结合位点，这表明它可能介导单核细胞对MCP-3的反应。然而，我们现在发现MCP-3是巨噬细胞炎性蛋白-1α（MIP-1α）/活化调节正常T细胞表达和分泌蛋白（RANTES）受体CC CKR1的配体和强效激动剂（[Ca2+]i变化的效价顺序为MIP-1α>MCP-3>RANTES），该受体在单核细胞>中性粒细胞>嗜酸性粒细胞中表达。125I-MCP-3直接与CC CKR1和CC CKR2B结合（Ki分别为8和7 nM）。除MCP-1外，所有测试的C-C趋化因子都能竞争与CC CKR1的结合。相反，只有MCP-3和MCP-1能竞争与CC CKR2B的结合。MCP-1和MCP-3都是等效激动剂（[Ca2+]i变化的EC50 = 1050）。因此，MCP-3是CC CKR1和CC CKR2B的功能性配体，而这两种受体对C-C趋化因子具有不同的选择性。这些数据表明，单核细胞对MCP-3的反应可能由CC CKR2B和CC CKR1介导，而嗜酸性粒细胞对MCP-3的反应可能由CC CKR1介导。
