ACTIONS OF THE CHEMOTACTIC CYTOKINES MCP-1, MCP-2, MCP-3, RANTES, MIP-1-ALPHA AND MIP-1-BETA ON HUMAN MONOCYTES
ACTIONS OF THE CHEMOTACTIC CYTOKINES MCP-1, MCP-2, MCP-3, RANTES, MIP-1-ALPHA AND MIP-1-BETA ON HUMAN MONOCYTES
复制标题
DOI：
10.1002/eji.1830250113
复制
发表时间：
1995-01-01
影响因子：
5.4
通讯作者：
BAGGIOLINI, M
中科院分区：
文献类型：
--
作者：
UGUCCIONI, M;DAPUZZO, M;BAGGIOLINI, M
研究了合成的6种CC趋化因子MCP-1、MCP-2、MCP-3、RANTES、MIP-1 α和MIP-1 β对人血液单核细胞的活性。所有CC趋化因子在体外诱导双峰迁移反应。单核细胞趋化蛋白（MCP）和RANTES的迁移细胞数量最多，MTP-1 α的迁移细胞数量略少，MIP-1 β的迁移细胞数量较弱。引诱剂以MCP-1和MIP-1 α最强，在0.1 ~ 1 nM处引诱效果最大。所有CC趋化因子也诱导细胞松弛素b预处理的单核细胞释放n -乙酰- β - d -氨基葡萄糖酶。MCP是最有效的（MCP-1 > MCP-3 > MCP-2）， RANTES和MIP-1 α显示中等（MCP-1活性的1/3），MIP-1 β只有最小活性。胞质游离Ca2+变化和胞吐监测受体脱敏。MCP-1、MCP-2和MCP-3与RANTES、MIP-1 α和MIP-1 β之间存在明显的交叉脱敏现象，表明CC趋化因子在这两个亚组中具有受体共享性。对RANTES、MIP-1 α和MIP-1 β的反应也被MCP-1、MCP-2或MCP-3预处理中度至显著脱敏，而对MCP的反应几乎不受RANTES、MIP-1 α和MIP-1 β预处理的影响。这些结果表明，MCP也与RANTES识别的受体、MIP-1 α和MIP-1 β相互作用，反之则不相互作用。用放射性标记的MCP-1或MIP-1 α进行结合研究。所有MCP很容易与标记的MCP-1竞争，产生浓度依赖的s型位移曲线。用RANTES、MIP-1 α和MIP-1 β在较高浓度下观察到位移，但不完全。放射性标记的MIP-1 α被MIP-1 α或MIP-1 β有效取代，但仅部分被RANTES取代。在MCP中，只有MC-3完全取代了MIP-1 α，而MCP-1和MCP-2只观察到部分取代。
The activities of six synthetic CC chemokines, MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta on human blood monocytes were studied. All CC chemokines elicited a bimodal migration response in vitro. Highest numbers of migrating cells were obtained with the monocyte chemotactic proteins (MCP) and RANTES, somewhat lower numbers with MTP-1 alpha, and only weak migration with MIP-1 beta. The most potent attractants were MCP-1 and MIP-1 alpha which reached maximum efficacy at 0.1 to 1 nM. All CC chemokines also induced the release of N-acetyl-beta-D-glucosaminidase from cytochalasin B-pretreated monocytes. The MCP were most effective (MCP-1 > MCP-3 > MCP-2), RANTES and MIP-1 alpha showed moderate (1/3 of MCP-1 activity), and MIP-1 beta only minimal activity. Cytosolic free Ca2+ changes and exocytosis were used to monitor receptor desensitization. Marked cross-desensitization was observed among MCP-1, MCP-2 and MCP-3 on the one hand, and RANTES, MIP-1 alpha and MIP-1 beta on the other, indicating receptor sharing within these two subgroups of CC chemokines. The responses to RANTES, MIP-1 alpha and MIP-1 beta were also moderately to markedly desensitized by pretreatment with MCP-1, MCP-2 or MCP-3,while the responses to the MCP were virtually unaffected by pretreatment with RANTES, MIP-1 alpha and MIP-1 beta. These results suggest that the MCP also interact with receptors recognized by RANTES, MIP-1 alpha and MIP-1 beta, but not vice versa. Binding studies were performed with radiolabeled MCP-1 or MIP-1 alpha. All MCP competed readily for labeled MCP-1 yielding a concentration-dependent sigmoidal displacement curve. Displacement with RANTES, MIP-1 alpha and MIP-1 beta was observed at higher concentrations, but was not complete. Radiolabeled MIP-1 alpha was displaced efficiently by MIP-1 alpha or MIP-1 beta, but only partially by RANTES. Of the MCP, only MC-3 completely displaced MIP-1 alpha, while only partial displacement was observed with MCP-1 and MCP-2.