HUMAN AND BOVINE GRANULOCYTE CHEMOTACTIC PROTEIN-2 - COMPLETE AMINO-ACID-SEQUENCE AND FUNCTIONAL-CHARACTERIZATION AS CHEMOKINES
HUMAN AND BOVINE GRANULOCYTE CHEMOTACTIC PROTEIN-2 - COMPLETE AMINO-ACID-SEQUENCE AND FUNCTIONAL-CHARACTERIZATION AS CHEMOKINES
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DOI：
10.1021/bi00089a037
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发表时间：
1993-09-28
期刊：
影响因子：
2.9
通讯作者：
VANDAMME, J
中科院分区：
文献类型：
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作者：
PROOST, P;WUYTS, A;VANDAMME, J
肿瘤细胞能够同时产生许多相关的炎症肽，现在被归类为趋化因子。我们分离出一种新的人粒细胞趋化蛋白 (GCP-2)，它是由骨肉瘤细胞与白细胞介素 8 (GCP-1/IL-8) 共同产生的。此外，使用相同的分离程序从肾肿瘤细胞中纯化人 GCP-2 的牛同源物。 两种趋化因子均以至少四种 NH2 末端截短的形式出现。使用标准体外迁移测定，这些 5-6-kDa 蛋白作为粒细胞趋化因子的效力和功效没有差异。通过对源自天然蛋白质的肽片段进行测序，揭示了人和牛 GCP-2 的完整一级结构。基于四个半胱氨酸残基的保守性，这两个分子被归类为 C-X-C 趋化因子家族，包括 IL-8。人和牛 GCP-2 在氨基酸水平上相似 67%。它们的序列与 IL-8 的序列仅有微弱的相似性，并且人 GCP-2 在 IL-8 的放射免疫测定中不会发生交叉反应。 人和牛 GCP-2 是特异性粒细胞趋化因子，因为它们不吸引人单核细胞。牛 GCP-2 不具有物种特异性，因为它对人粒细胞的活性至少与人 GCP-2 一样。两种趋化因子还可激活受体后机制，导致粒细胞释放明胶酶 B。这表明在炎症和肿瘤细胞侵袭中可能发挥作用。
Tumor cells are capable of simultaneously producing a number of related inflammatory peptides, now classified as chemokines. We have isolated a new human granulocyte chemotactic protein (GCP-2), coproduced with interleukin-8 (GCP-1/IL-8) by osteosarcoma cells. Furthermore, the bovine homologue of human GCP-2 was purified from kidney tumor cells using the same isolation procedure. Both chemokines occur in at least four NH2-terminally truncated forms. These 5-6-kDa proteins do not differ in potency and efficacy as granulocyte chemotactic factors using a standard in vitro migration assay. The complete primary structures of human and bovine GCP-2 were disclosed by sequencing peptide fragments derived from the natural proteins. On the basis of the conservation of four cysteine residues, the two molecules are to be classified within the C-X-C chemokine family, including IL-8. Human and bovine GCP-2 are 67% similar at the amino acid level. Their sequences show only weak similarity with that of IL-8, and human GCP-2 does not cross-react in a radioimmunoassay for IL-8. Human and bovine GCP-2 are specific granulocyte chemotactic factors in that they do not attract human monocytes. Bovine GCP-2 is not species specific since it is at least as active as human GCP-2 on human granulocytes. Both chemokines can also activate postreceptor mechanisms leading to release of gelatinase B by granulocytes. This is indicative for a possible role in inflammation and tumor cell invasion.