Ohno I, Lea R, Finotto S, Marshall J, Denburg J, Dolovich J, Gauldie J, Jordana M
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Am J Respir Cell Mol Biol. 1991 Dec;5(6):505-10. doi: 10.1165/ajrcmb/5.6.505.
Nasal polyposis is a chronic inflammatory condition of the upper airways characterized by infiltration of activated inflammatory cells, particularly eosinophils. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a cytokine with powerful biologic effects including the regulation of survival, proliferation, and activation of granulocytes as well as differentiation of hemopoietic cells. To examine the potential role of GM-CSF in the pathogenesis of this condition, we investigated gene expression and production of GM-CSF in nasal polyp tissues as well as in the normal nasal mucosa. Immunoreactive GM-CSF was detected by enzyme-linked immunosorbent assay in the 24-h supernatant of nasal polyp tissues placed in culture. By Northern blot analysis and Southern blot analysis following a reverse-transcription polymerase chain reaction using a human GM-CSF cDNA probe, we detected GM-CSF mRNA in nasal polyp tissues, as well as in the tissue from a patient with allergic rhinitis, but not in the normal nasal mucosa. By in situ hybridization using the same probe, cells expressing mRNA specific for GM-CSF were observed in nasal polyp tissues and in the allergic nasal mucosa. In addition, by the combination of in situ hybridization and counterstaining with chromotrope 2R, we demonstrated that approximately 30% of eosinophils infiltrating the polyp tissue express the GM-CSF gene. These results suggest a novel mechanism by which eosinophils may contribute to the pathogenesis of chronic inflammatory diseases such as nasal polyposis, allergic rhinitis, and, by implication, asthma.
鼻息肉病是上呼吸道的一种慢性炎症性疾病,其特征是有活化的炎症细胞浸润,尤其是嗜酸性粒细胞。粒细胞/巨噬细胞集落刺激因子(GM-CSF)是一种具有强大生物学效应的细胞因子,包括调节粒细胞的存活、增殖和活化以及造血细胞的分化。为了研究GM-CSF在这种疾病发病机制中的潜在作用,我们调查了鼻息肉组织以及正常鼻黏膜中GM-CSF的基因表达和产生情况。通过酶联免疫吸附测定法在培养的鼻息肉组织24小时培养上清液中检测到免疫反应性GM-CSF。使用人GM-CSF cDNA探针进行逆转录聚合酶链反应后,通过Northern印迹分析和Southern印迹分析,我们在鼻息肉组织以及变应性鼻炎患者的组织中检测到GM-CSF mRNA,但在正常鼻黏膜中未检测到。使用相同探针进行原位杂交,在鼻息肉组织和变应性鼻黏膜中观察到表达GM-CSF特异性mRNA的细胞。此外,通过原位杂交与铬变素2R复染相结合,我们证明浸润息肉组织的嗜酸性粒细胞中约30%表达GM-CSF基因。这些结果提示了一种新的机制,通过该机制嗜酸性粒细胞可能参与鼻息肉病、变应性鼻炎以及由此推断的哮喘等慢性炎症性疾病的发病过程。