Receptor binding specificity and pulmonary gene expression of the neutrophil-activating peptide ENA-78
Receptor binding specificity and pulmonary gene expression of the neutrophil-activating peptide ENA-78
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DOI：
10.1165/ajrcmb.14.3.8845182
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发表时间：
1996-03-01
影响因子：
6.4
通讯作者：
Gerard, C
中科院分区：
文献类型：
--
作者：
Bozic, CR;Gerard, NP;Gerard, C
中性粒细胞激活肽ENA-78是从人II型肺上皮细胞系中分离的一种新型趋化细胞因子。它是促炎多肽趋化因子家族的成员，与白细胞介素-8（IL-8）和GRO α具有结构同源性。牛肺炎肺肺泡白细胞中ENA-78的免疫组化鉴定支持ENA-78在肺部炎症的发病机制中的作用。虽然ENA-78能够刺激多形核中性粒细胞（PMN），但其结合特异性及其在人类肺部疾病状态中的表达均未确定。I-125标记的ENA-78与人PMN具有高亲和力结合。其对PMN的作用似乎是由IL-8 B型受体介导的，其与IL-8 B型受体结合的Kd为2.2 nM。人IL-8、GRO α和鼠KC以高亲和力竞争I-125-ENA-78与人IL-8 B型受体的结合。相反，I-125-ENA-78不与IL-8 A型受体结合，也不显著竞争I-125-IL-8与该相同受体的结合。ENA-78是Mac-1细胞表面表达的有效上调剂。此外，在囊性纤维化肺中检测到ENA-78 mRNA，但在正常供体肺中未检测到。因此，ENA-78 mRNA水平似乎在人肺部炎症中增加，其对PMN的刺激活性似乎主要由IL-8 B型受体介导。
Neutrophil-activating peptide ENA-78 is a novel chemotactic cytokine isolated from a human type II pulmonary epithelial cell line. It is a member of the chemokine family of proinflammatory polypeptides and exhibits structural homology to interleukin-8 (IL-8) and GRO alpha. The immunohistochemical identification of ENA-78 in pulmonary alveolar leukocytes of bovine pneumonic lungs supports a role for ENA-78 in the pathogenesis of pulmonary inflammation. Although ENA-78 is able to stimulate polymorphonuclear neutrophils (PMN), neither its binding specificities nor its expression in human pulmonary disease states have been determined. I-125-labeled ENA-78 binds with high affinity to human PMN. Its actions on PMN appear to be mediated by the IL-8 type B receptor, to which it binds with a K-d of 2.2 nM. Human IL-8, GRO alpha, and murine KC compete with high affinity for I-125-ENA-78 binding to the human IL-8 type B receptor. In contrast, I-125-ENA-78 does not bind to the IL-8 type A receptor nor does it compete significantly for I-125-IL-8 binding to this same receptor. ENA-78 is a potent upregulator of Mac-1 cell surface expression. In addition, ENA-78 mRNA is detected in cystic fibrosis lung but is not detected in normal donor lung. Thus, ENA-78 mRNA levels appear to be increased in human pulmonary inflammation and its stimulatory activities on PMN appear to be a function mediated primarily by the IL-8 type B receptor.