Inoue Yoshinari, Matsuwaki Yoshinori, Shin Seung-Heon, Ponikau Jens U, Kita Hirohito
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
J Immunol. 2005 Oct 15;175(8):5439-47. doi: 10.4049/jimmunol.175.8.5439.
Eosinophils and their products are probably important in the pathophysiology of allergic diseases, such as bronchial asthma, and in host immunity to certain organisms. An association between environmental fungal exposure and asthma has been long recognized clinically. Although products of microorganisms (e.g., lipopolysaccharides) directly activate certain inflammatory cells (e.g., macrophages), the mechanism(s) that triggers eosinophil degranulation is unknown. In this study we investigated whether human eosinophils have an innate immune response to certain fungal organisms. We incubated human eosinophils with extracts from seven environmental airborne fungi (Alternaria alternata, Aspergillus versicolor, Bipolaris sorokiniana, Candida albicans, Cladosporium herbarum, Curvularia spicifera, and Penicillium notatum). Alternaria and Penicillium induced calcium-dependent exocytosis (e.g., eosinophil-derived neurotoxin release) in eosinophils from normal individuals. Alternaria also strongly induced other activation events in eosinophils, including increases in intracellular calcium concentration, cell surface expression of CD63 and CD11b, and production of IL-8. Other fungi did not induce eosinophil degranulation, and Alternaria did not induce neutrophil activation, suggesting specificity for fungal species and cell type. The Alternaria-induced eosinophil degranulation was pertussis toxin sensitive and desensitized by preincubating cells with G protein-coupled receptor agonists, platelet-activating factor, or FMLP. The eosinophil-stimulating activity in Alternaria extract was highly heat labile and had an M(r) of approximately 60 kDa. Thus, eosinophils, but not neutrophils, possess G protein-dependent cellular activation machinery that directly responds to an Alternaria protein product(s). This innate response by eosinophils to certain environmental fungi may be important in host defense and in the exacerbation of inflammation in asthma and allergic diseases.
嗜酸性粒细胞及其产物可能在过敏性疾病（如支气管哮喘）的病理生理学以及宿主对某些生物体的免疫中发挥重要作用。临床上长期以来一直认识到环境中真菌暴露与哮喘之间的关联。尽管微生物产物（如脂多糖）可直接激活某些炎症细胞（如巨噬细胞），但触发嗜酸性粒细胞脱颗粒的机制尚不清楚。在本研究中，我们调查了人类嗜酸性粒细胞对某些真菌生物体是否具有先天性免疫反应。我们将人类嗜酸性粒细胞与七种环境空气传播真菌（链格孢、杂色曲霉、索氏麦角菌、白色念珠菌、草本枝孢、穗状弯孢霉和青霉）的提取物一起孵育。链格孢和青霉可诱导正常个体嗜酸性粒细胞发生钙依赖性胞吐作用（如嗜酸性粒细胞衍生神经毒素释放）。链格孢还强烈诱导嗜酸性粒细胞发生其他激活事件，包括细胞内钙浓度增加、CD63和CD11b细胞表面表达增加以及IL-8产生。其他真菌未诱导嗜酸性粒细胞脱颗粒，链格孢也未诱导中性粒细胞激活，这表明对真菌种类和细胞类型具有特异性。链格孢诱导的嗜酸性粒细胞脱颗粒对百日咳毒素敏感，并且通过用G蛋白偶联受体激动剂、血小板活化因子或FMLP预孵育细胞而脱敏。链格孢提取物中的嗜酸性粒细胞刺激活性对热高度不稳定，分子量约为60 kDa。因此，嗜酸性粒细胞而非中性粒细胞具有直接响应链格孢蛋白产物的G蛋白依赖性细胞激活机制。嗜酸性粒细胞对某些环境真菌的这种先天性反应可能在宿主防御以及哮喘和过敏性疾病炎症的加剧方面具有重要意义。
