Platelet-derived chemokines CXC chemokine ligand (CXCL)7, connective tissue-activating peptide III, and CXCL4 differentially affect and cross-regulate neutrophil adhesion and transendothelial migration
Platelet-derived chemokines CXC chemokine ligand (CXCL)7, connective tissue-activating peptide III, and CXCL4 differentially affect and cross-regulate neutrophil adhesion and transendothelial migration
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DOI：
10.4049/jimmunol.169.5.2602
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发表时间：
2002-09-01
影响因子：
4.4
通讯作者：
Brandt, E
中科院分区：
文献类型：
--
作者：
Schenk, BI;Petersen, F;Brandt, E
在这项研究中，我们研究了主要的血小板衍生的CXC趋化因子结缔组织激活肽III（CTAP-III），其截短产物嗜中性粒细胞激活肽2（CXC趋化因子配体7（CXCL 7）），以及结构相关的血小板因子4（CXCL 4）对中性粒细胞粘附和穿越未受刺激的血管内皮细胞的影响。使用单层培养的HUVEC，我们发现所有三种趋化因子促进中性粒细胞粘附，而只有CXCL 7诱导迁移。CTAP-III是一种迄今为止被描述为缺乏嗜中性粒细胞刺激能力的分子，暴露于CTAP-III后细胞粘附的诱导依赖于中性粒细胞将非活性趋化因子蛋白水解转化为CXCL 7。这从CTAP-III加工蛋白酶的抑制和CXCL 7高亲和力受体CXCR-2的同时阻断导致CTAP-III介导的嗜中性粒细胞粘附的完全消除的实验中是明显的。CXCL 4在亚刺激剂量调制CTAP-III-以及CXCL 7诱导的粘附。虽然细胞粘附暴露于CTAP-III后急剧减少，CXCL 7介导的粘附进行了显着的增强。中性粒细胞响应CXCL 7或IL-8（CXCL 8）的跨内皮迁移受到CTAP-III的调节，但不受CXCL 4的调节，如通过预先暴露于CTAP-III的中性粒细胞的迁移反应的急剧脱敏所观察到的，这被CXCR-2的选择性下调所抑制。总之，我们的研究结果表明，血小板衍生的趋化因子之间存在着多种相互作用的调节中性粒细胞粘附和跨内皮迁移。
In this study, we have examined the major platelet-derived CXC chemokines connective tissue-activating peptide III (CTAP-III), its truncation product neutrophil-activating peptide 2 (CXC chemokine ligand 7 (CXCL7)), as well as the structurally related platelet factor 4 (CXCL4) for their impact on neutrophil adhesion to and transmigration through unstimulated vascular endothelium. Using monolayers of cultured HUVEC, we found all three chemokines to promote neutrophil adhesion, while only CXCL7 induced transmigration. Induction of cell adhesion following exposure to CTAP-III, a molecule to date described to lack neutrophil-stimulating capacity, depended on proteolytical conversion of the inactive chemokine into CXCL7 by neutrophils. This was evident from experiments in which inhibition of the CTAP-III-processing protease and simultaneous blockade of the CXCL7 high affinity receptor CXCR-2 led to complete abrogation of CTAP-III-mediated neutrophil adhesion. CXCL4 at substimulatory dosages modulated CTAP-III- as well as CXCL7-induced adhesion. Although cell adhesion following exposure to CTAP-III was drastically reduced, CXCL7-mediated adhesion underwent significant enhancement. Transendothelial migration of neutrophils in response to CXCL7 or IL-8 (CXCL8) was subject to modulation by CTAP-III, but not CXCL4, as seen by drastic desensitization of the migratory response of neutrophils pre-exposed to CTAP-III, which was paralleled by selective down-modulation of CXCR-2. Altogether our results demonstrate that there exist multiple interactions between platelet-derived chemokines in the regulation of neutrophil adhesion and transendothelial migration.