A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes.
A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes.
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DOI：
10.4049/jimmunol.159.3.1140
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发表时间：
1997-08
影响因子：
4.4
通讯作者：
K. Hieshima;Toshio Imai;Masataka Baba;K. Shoudai;K. Ishizuka;T. Nakagawa;J. Tsuruta;M. Takeya;Y. Sakaki;K. Takatsuki;R. Miura;G. Opdenakker;J. Damme;O. Yoshie;H. Nomiyama
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作者：
K. Hieshima;Toshio Imai;Masataka Baba;K. Shoudai;K. Ishizuka;T. Nakagawa;J. Tsuruta;M. Takeya;Y. Sakaki;K. Takatsuki;R. Miura;G. Opdenakker;J. Damme;O. Yoshie;H. Nomiyama
通过搜索表达序列标签（EST）数据库，我们鉴定了编码与人CC趋化因子巨噬细胞炎症蛋白-1α（MIP-1α）/LD78α具有显着序列同一性的多肽的部分cDNA序列。我们确定了包含 89 个氨基酸的阅读框的完整 cDNA 序列，与人 MIP-1 α/LD78 α 具有 61% 的同一性。该mRNA在人肺中高水平表达，在一些淋巴组织中低水平表达。此外，PMA 在几种人类细胞系（包括单核细胞 U937 细胞）中强烈诱导 mRNA。根据这些结果，我们将这种新型 CC 趋化因子命名为 PARC，来自肺部和活化调节趋化因子。原位杂交分析表明，LPS刺激的肺泡巨噬细胞、区域淋巴结生发中心的滤泡树突状细胞和外周血单核细胞表达PARC mRNA。使用我们最近构建的人类 CC 趋化因子酵母人工染色体重叠群，我们将 PARC 基因 (SCYA18) 定位在染色体 17q11.2 的 CC 趋化因子基因簇的两个子区域之一内。为了研究其生物活性，PARC 蛋白在昆虫细胞中表达。 PARC 对活化的 (CD3+) T 细胞和非活化的 (CD14-) 淋巴细胞都有趋化作用，但对单核细胞或粒细胞没有趋化作用。使用与碱性磷酸酶-(His)6 融合的 PARC 进行的结合分析表明，淋巴细胞上存在一类 PARC 受体，Kd 为 1.9 nM，每个细胞有 590 个位点。因此，PARC是一种新型CC趋化因子，与MIP-1α/LD78α具有密切的系统发育关系，但对淋巴细胞具有高度选择性活性。
By searching the expressed sequence tag (EST) database, we identified partial cDNA sequences encoding a polypeptide with significant sequence identity to the human CC chemokine macrophage-inflammatory protein-1 alpha (MIP-1 alpha)/LD78 alpha. We determined the complete cDNA sequence that contained a reading frame of 89 amino acids with 61% identity to human MIP-1 alpha/LD78 alpha. The mRNA was expressed constitutively at high levels in human lung and at low levels in some lymphoid tissues. Furthermore, the mRNA was strongly induced in several human cell lines, including monocytic U937 cells, by PMA. From these results, we designated this novel CC chemokine as PARC from pulmonary and activation-regulated chemokine. In situ hybridization analyses showed that alveolar macrophages, follicular dendritic cells in the germinal centers of regional lymph nodes, and peripheral blood monocytes stimulated with LPS express PARC mRNA. Using the human CC chemokine yeast artificial chromosome contig that we constructed recently, we mapped the PARC gene (SCYA18) within one of the two subregions of the CC chemokine gene cluster at chromosome 17q11.2. To investigate its biologic activity, the PARC protein was expressed in insect cells. PARC was chemotactic for both activated (CD3+) T cells and nonactivated (CD14-) lymphocytes, but not for monocytes or granulocytes. Binding analysis using PARC fused with alkaline phosphatase-(His)6 showed the presence of a single class of receptors for PARC on lymphocytes with a Kd of 1.9 nM and 590 sites/cell. Thus, PARC is a novel CC chemokine with a close phylogenic relationship with MIP-1 alpha/LD78 alpha, but with a highly selective activity on lymphocytes.