Macrophage inflammatory protein-1 alpha influences eosinophil recruitment in antigen-specific airway inflammation.
Macrophage inflammatory protein-1 alpha influences eosinophil recruitment in antigen-specific airway inflammation.
复制标题
巨噬细胞炎症蛋白 1 α 影响抗原特异性气道炎症中嗜酸性粒细胞的募集。
DOI：
10.1002/eji.1830250140
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Kunkel,SL
中科院分区：
文献类型：
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作者：
Lukacs,NW;Strieter,RM;Shaklee,CL;Chensue,SW;Kunkel,SL
变应性气道炎症的特征在于肺气道粘膜下层内的支气管周围嗜酸性粒细胞积聚。在本研究中，我们利用了一个气道炎症模型，由肠道内攻击与寄生虫（血吸虫）曼氏卵抗原（SEA）在致敏小鼠。嗜中性粒细胞和嗜酸性粒细胞进入气道的募集分别在激发后8和48 h达到最大。由于巨噬细胞炎性蛋白-1 α（MIP-1α）先前已被发现在体外对嗜酸性粒细胞具有趋化性，因此我们假设MIP-1α参与气道炎症，更具体地说，参与嗜酸性粒细胞向气道的募集。初步研究表明，与溶剂处理的对照小鼠相比，SEA激发后8 h MIP-1α mRNA表达增加。接下来，我们证明了与对照激发小鼠相比，SEA激发小鼠肺中MIP-1α蛋白在8 h时显著增加，与mRNA数据相关。SEA激发小鼠肺的免疫组织化学染色显示，MIP-1α蛋白在气道上皮细胞、肺泡巨噬细胞和募集的单核细胞群中表达。MIP-1α对支气管肺泡灌洗液中细胞的免疫定位表明，巨噬细胞和嗜酸性粒细胞对该蛋白染色呈阳性。为了确定MIP-1α表达对嗜酸性粒细胞蓄积的贡献，在气管内SEA攻击前3-4小时，用中和MIP-1α抗体或正常兔IgG被动免疫SEA攻击的小鼠。这些研究表明，在接受中和MIP-1α抗体的动物中，肺和气道嗜酸性粒细胞募集减少> 50%，对早期中性粒细胞募集无影响。这些结果表明，由抗原特异性反应诱导的MIP-1α的产生在该气道炎症模型中嗜酸性粒细胞的募集中起重要作用。
Allergic airway inflammation is characterized by peribronchial eosinophil accumulation within the submucosa of the airway of the lung. In the present study we have utilized a model of airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg antigen (SEA) in presensitized mice. The recruitment of neutrophils and eosinophils into the airway was found to be maximal at 8 and 48 h post challenge, respectively. Since macrophage inflammatory protein‐1α (MIP‐1α) has previously been found to be chemotactic for eosinophils,in vitro, we postulated that MIP‐1α was involved in the airway inflammation and more specifically in eosinophil recruitment into the airway. Initial studies demonstrated an increase in MIP‐1α mRNA expression at 8 h post‐SEA challenge, as compared to vehicle‐treated control mice. We next demonstrated a significant increase in MIP‐1α protein in the lungs of SEA‐challenged mice at 8 h compared to control challenged mice, correlating to the mRNA data. Immunohistochemical staining of lungs from SEA‐challenged mice demonstrated MIP‐1α protein expression in airway epithelial cells, alveolar macrophages and in recruited mononuclear cell populations. Immunolocalization of MIP‐1α to cells within the bronchoalveolar lavage fluid demonstrated that macrophages and eosinophils stained positive for the protein. To determine the contribution of MIP‐1α expression to eosinophil accumulation, SEA‐challenged mice were passively immunized with either neutralizing MIP‐1α antibodies or normal rabbit IgG, 3–4 h prior to the intratracheal SEA challenge. These studies demonstrated a > 50% decrease in eosinophil recruitment to the lungs and airway in animals receiving neutralizing MIP‐1α antibodies with no effect on early neutrophil recruitment. These results suggest that the production of MIP‐1α, induced by an antigen‐specific response, plays an important role in recruitment of eosinophils in this airway model of inflammation.