Ahn Mi-Hyun, Kang Chun-Mi, Park Choon-Sik, Park Sang-Jun, Rhim Taiyoun, Yoon Pyeong-Oh, Chang Hun Soo, Kim Soo-Ho, Kyono Hiroko, Kim Kwang Chul
Genome Research Center for Allergy and Respiratory disease, Soonchunhyang University Hospital, Bucheon, Korea.
Respir Res. 2005 Apr 13;6(1):34. doi: 10.1186/1465-9921-6-34.
Inhalation of particles aggravates respiratory symptoms including mucus hypersecretion in patients with chronic airway disease and induces goblet cell hyperplasia (GCH) in experimental animal models. However, the underlying mechanisms remain poorly understood.
To understand this, the numbers of goblet cells, Muc5ac (+) expressing epithelial cells and IL-13 expressing mast cells were measured in the trachea of sham or TiO2 particles-treated rats using periodic acid-Schiff, toluidine blue and immunohistochemical staining. RT-PCR for Muc-1, 2 and 5ac gene transcripts was done using RNA extracted from the trachea. Differential cell count and IL-13 levels were measured in bronchoalveolar lavage (BAL) fluid. In pretreatment groups, cyclophosphamide (CPA) or dexamethasone (DEX) was given before instillation of TiO2. TiO2 treatment markedly increased Muc5ac mRNA expression, and Muc5ac (+) or PAS (+) epithelial cells 48 h following treatment.
The concentration of IL-13 in BAL fluids was higher in TiO2 treated-rats when compared to those in sham rats (p < 0.05). Pretreatment with cyclophosphamide (CPA) decreased the number of neutrophils and eosinophils in BAL fluid of TiO2 treated-rats (p < 0.05), but affected neither the percentage of PAS (+) cells, nor IL-13 levels in the BAL fluids (p > 0.05). In contrast, pretreatment with dexamethasone (DEX) diminished the percentage of PAS (+) cells and the levels of IL-13 (p < 0.05). TiO2 treatment increased the IL-13 (+) mast cells (p < 0.05) in the trachea, which was suppressed by DEX (p < 0.05), but not by CPA pretreatment (p > 0.05). In addition there were significant correlations of IL-13 (+) rate of mast cells in the trachea with IL-13 concentration in BAL fluid (p < 0.01) and with the percentage of Muc5ac (+) cells in the sham and TiO2 treated rats (p < 0.05).
In conclusion, TiO2 instillation induces GCH and Muc5ac expression, and this process may be associated with increased production of IL-13 by mast cells.
吸入颗粒物会加重慢性气道疾病患者的呼吸道症状，包括黏液分泌过多，并在实验动物模型中诱导杯状细胞增生（GCH）。然而，其潜在机制仍知之甚少。
为了解这一情况，使用过碘酸希夫氏染色、甲苯胺蓝染色和免疫组织化学染色法，对假手术组或二氧化钛颗粒处理组大鼠气管中的杯状细胞、表达Muc5ac的上皮细胞和表达白细胞介素-13（IL-13）的肥大细胞数量进行了检测。使用从气管中提取的RNA对Muc-1、2和5ac基因转录本进行逆转录聚合酶链反应（RT-PCR）。对支气管肺泡灌洗（BAL）液进行细胞分类计数并检测IL-13水平。在预处理组中，在滴注二氧化钛之前给予环磷酰胺（CPA）或地塞米松（DEX）。二氧化钛处理显著增加了Muc5ac mRNA表达以及处理后48小时的Muc5ac（+）或过碘酸希夫氏阳性（PAS（+））上皮细胞数量。
与假手术组大鼠相比，二氧化钛处理组大鼠BAL液中的IL-13浓度更高（p < 0.05）。用环磷酰胺（CPA）预处理可减少二氧化钛处理组大鼠BAL液中的中性粒细胞和嗜酸性粒细胞数量（p < 0.05），但对PAS（+）细胞百分比和BAL液中的IL-13水平均无影响（p > 0.05）。相比之下，用地塞米松（DEX）预处理可降低PAS（+）细胞百分比和IL-13水平（p < 0.05）。二氧化钛处理增加了气管中IL-13（+）肥大细胞数量（p < 0.05），这一现象被DEX抑制（p < 0.05），但未被CPA预处理抑制（p > 0.05）。此外，气管中肥大细胞的IL-13（+）率与BAL液中的IL-13浓度（p < 0.01）以及假手术组和二氧化钛处理组大鼠中Muc5ac（+）细胞百分比均存在显著相关性（p < 0.05）。
总之，滴注二氧化钛可诱导杯状细胞增生和Muc5ac表达，这一过程可能与肥大细胞IL-13产生增加有关。
