EVIDENCE OF A ROLE FOR MESOTHELIAL CELL-DERIVED INTERLEUKIN-8 IN THE PATHOGENESIS OF ASBESTOS-INDUCED PLEURISY IN RABBITS
EVIDENCE OF A ROLE FOR MESOTHELIAL CELL-DERIVED INTERLEUKIN-8 IN THE PATHOGENESIS OF ASBESTOS-INDUCED PLEURISY IN RABBITS
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DOI：
10.1172/jci115710
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发表时间：
1992-04-01
影响因子：
15.9
通讯作者：
BROADDUS, VC
中科院分区：
文献类型：
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作者：
BOYLAN, AM;RUEGG, C;BROADDUS, VC
虽然石棉引起的急性胸膜炎的特点是中性粒细胞大量涌入，但吸引这些细胞进入胸膜腔的因素及其来源尚不清楚。我们发现，兔胸腔内滴入青石棉可引起胸液中出现中性粒细胞趋化活性，且这种趋化活性可被人白介素8(IL-8)中和抗体显著抑制。青石棉培养的兔胸膜间皮细胞也能释放中性粒细胞趋化活性，这种趋化活性可被抗IL-8抗体显著抑制。为了确定兔胸膜间皮细胞是否能合成IL-8，我们根据人和绵羊IL-8基因的同源序列，通过聚合酶链式反应(PCR)扩增胸膜间皮细胞的c DNA，并根据人和羊的IL-8 cDNAs的同源序列，构建了兔IL-8基因的探针。以同源性为基础的聚合酶链式反应扩增出单一的cDNA片段，其核苷酸序列与人IL-8基因相应区域的核苷酸序列同源性为88%。以放射性标记的聚合酶链式反应产物为探针，我们证实了石棉对胸膜间皮细胞IL-8mRNA表达的快速诱导作用。不出所料，肿瘤坏死因子-α还导致了IL-8在兔胸膜腔内的出现，并刺激培养的胸膜间皮细胞合成和释放IL-8。结论：石棉可直接刺激胸膜间皮细胞合成IL-8，间皮细胞来源的IL-8可能在石棉致胸膜炎症中起重要作用。
Although acute asbestos-induced pleurisy is characterized by an influx of neutrophils, the identity of the factors that attract these cells to the pleural space and the source of the factors are unknown. We found that instillation of crocidolite asbestos into the pleural space of rabbits led to the appearance in pleural liquid of chemotactic activity for neutrophils, and that this chemotatic activity was inhibited significantly by a neutralizing antibody to human interleukin 8 (IL-8). Cultured rabbit pleural mesothelial cells incubated with crocidolite asbestos also released chemotactic activity for neutrophils, which was inhibited significantly by the anti-IL-8 antibody. To determine whether rabbit pleural mesothelial cells synthesize IL-8, we generated a probe for rabbit IL-8 mRNA by amplifying cDNA prepared from stimulated pleural mesothelial cells using the polymerase chain reaction (PCR) and primers based on homologous sequences in human and sheep IL-8 cDNAs. Homology-based PCR yielded a single cDNA fragment with a nucleotide sequence 88% identical to that of a corresponding region of human IL-8 cDNA. With the radiolabeled PCR product as a probe, we demonstrated rapid induction of IL-8 mRNA expression in pleural mesothelial cells exposed to asbestos. As expected, tumor necrosis factor-alpha also led to the appearance of IL-8 in the rabbit pleural space and stimulated cultured pleural mesothelial cells to synthesize and release IL-8. We conclude that asbestos directly stimulates pleural mesothelial cells to synthesize IL-8 and that mesothelial cell-derived IL-8 may play an important role in mediating asbestos-induced pleural inflammation.