Gillitzer R, Ritter U, Spandau U, Goebeler M, Bröcker E B
Department of Dermatology, University of Wurzburg Medical School, Germany.
J Invest Dermatol. 1996 Nov;107(5):778-82. doi: 10.1111/1523-1747.ep12371803.
Dense focal accumulation of neutrophils in the upper epidermis is a hallmark of psoriasis. Because the signals for neutrophil diapedesis and migration in vivo are not fully understood, psoriatic lesions with pronounced migration of neutrophils may serve as an important model for studying neutrophil chemotaxis. In this study, we present evidence for differential expression of the neutrophil chemotactic cytokines growth-related oncogene alpha, interleukin-8, and ENA-78 (epithelial cell derived and neutrophil-activating properties, 78 amino acids) in psoriatic lesions. In situ hybridization and immunohistochemistry of serial sections were employed to identify and microanatomically localize the cells producing these chemokines. High levels of focal interleukin-8 message were found to be expressed in the upper epidermis by keratinocytes and, most importantly, neutrophils themselves. Growth-related oncogene alpha transcripts were detected in clusters of keratinocytes of the upper epidermis at the same sites where interleukin-8 mRNA was abundant. In contrast to interleukin-8, growth-related oncogene alpha was also detected in the papillary dermis produced by vessel-associated cells. Sites of interleukin-8 and growth-related oncogene alpha mRNA expression were associated with infiltration of neutrophils. Interestingly, mRNA expression of the highly homologous chemokine ENA-78 was quiescent. In conclusion, our data indicate that growth-related oncogene alpha is an important chemoattractant for neutrophil diapedesis in vivo, whereas further migration of neutrophils and formation of micropustules appears to be influenced by the cooperative action of both growth-related oncogene alpha and interleukin-8.
中性粒细胞在表皮上层的密集灶性聚集是银屑病的一个标志。由于体内中性粒细胞渗出和迁移的信号尚未完全明确，中性粒细胞有明显迁移的银屑病皮损可能是研究中性粒细胞趋化性的重要模型。在本研究中，我们提供了证据表明在银屑病皮损中，中性粒细胞趋化细胞因子生长相关癌基因α、白细胞介素-8和ENA-78（上皮细胞衍生且具有中性粒细胞激活特性，78个氨基酸）存在差异表达。采用连续切片的原位杂交和免疫组织化学方法来识别产生这些趋化因子的细胞并进行微观解剖定位。发现角质形成细胞以及最重要的是中性粒细胞自身在上表皮中高水平表达局灶性白细胞介素-8信息。在白细胞介素-8 mRNA丰富的相同部位，在上表皮的角质形成细胞簇中检测到生长相关癌基因α转录本。与白细胞介素-8不同，生长相关癌基因α也在血管相关细胞产生的乳头真皮中被检测到。白细胞介素-8和生长相关癌基因α mRNA表达位点与中性粒细胞浸润相关。有趣的是，高度同源的趋化因子ENA-78的mRNA表达处于静止状态。总之，我们的数据表明生长相关癌基因α是体内中性粒细胞渗出的重要趋化因子，而中性粒细胞的进一步迁移和微脓疱的形成似乎受生长相关癌基因α和白细胞介素-8协同作用的影响。
