Accumulation of peribronchial mast cells in a mouse model of ovalbumin allergen induced chronic airway inflammation: Modulation by immunostimulatory DNA sequences
Accumulation of peribronchial mast cells in a mouse model of ovalbumin allergen induced chronic airway inflammation: Modulation by immunostimulatory DNA sequences
复制标题
DOI：
10.4049/jimmunol.171.9.4860
复制
发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Broide, DH
中科院分区：
文献类型：
--
作者：
Ikeda, RK;Miller, M;Broide, DH
在未暴露小鼠的肺中或经吸入OVA急性激发的OVA致敏小鼠的肺中均观察到少量支气管周围肥大细胞。在这项研究中，我们证明，反复吸入OVA致敏小鼠1-6个月，支气管周围肥大细胞有显着的积累。支气管周围肥大细胞的这种积聚与Th 2细胞衍生的肥大细胞生长因子（包括IL-4和IL-9）的表达增加有关，但与非Th 2细胞衍生的肥大细胞生长因子（干细胞因子）无关。用含有CpG基序的DNA的免疫刺激序列（ISS）预处理小鼠显著抑制支气管周围肥大细胞的积累和IL-4和IL-9的表达。为了确定肥大细胞是否表达Toll样受体-9（TLR-9; ISS的受体），通过RT-PCR评估小鼠骨髓来源的肥大细胞（MBMMC）的TLR-9表达。MBMMCs强烈表达TLR-9并结合罗丹明标记的ISS。然而，MBMMC与ISS在体外孵育既不抑制NBMMC增殖，也不抑制Ag/IgE介导的MBMMC脱粒，但它们确实诱导IL-6。总体而言，这些研究表明，暴露于反复OVA攻击而非急性OVA攻击的小鼠具有支气管周围肥大细胞的积聚，并且在肺中表达增加水平的肥大细胞生长因子。虽然肥大细胞表达TLR-9，但ISS在体外不直接抑制肥大细胞增殖，表明ISS通过间接机制抑制支气管周围肥大细胞在体内的蓄积，包括抑制Th 2细胞衍生的肥大细胞生长因子的肺表达。
Few peribronchial mast cells are noted either in the lungs of naive mice or in the lungs of OVA-sensitized mice challenged acutely with OVA by inhalation. In this study, we demonstrate that OVA-sensitized mice exposed to repetitive OVA inhalation for 1-6 mo have a significant accumulation of peribronchial mast cells. This accumulation of peribronchial mast cells is associated with increased expression of the Th2 cell-derived mast cell growth factors, including IL-4 and IL-9, but not with the non-Th2 cell-derived mast cell growth factor, stem cell factor. Pretreating mice with immunostimulatory sequences (ISS) of DNA containing a CpG motif significantly inhibited the accumulation of peribronchial mast cells and the expression of IL-4 and IL-9. To determine whether mast cells express Toll-like receptor-9 (TLR-9; the receptor for ISS), TLR-9 expression by mouse bone marrow-derived mast cells (MBMMCs) was assessed by RT-PCR. MBMMCs strongly expressed TLR-9 and bound rhodamine-labeled ISS. However, incubation of MBMMCs with ISS in vitro neither inhibited NBMMC proliferation nor inhibited Ag/IgE-mediated MBMMC degranulation, but they did induce IL-6. Overall these studies demonstrate that mice exposed to repetitive OVA challenge, but not acute OVA challenge, have an accumulation of peribronchial mast cells and express increased levels of mast cell growth factors in the lung. Although mast cells express TLR-9, ISS does not directly inhibit mast cell proliferation in vitro, suggesting that ISS inhibits accumulation of peribronchial mast cells in vivo by indirect mechanism(s), which include inhibiting the lung expression of Th2 cell-derived mast cell growth factors.