哮喘联盟

   摘要
   背景：外来体指参与细胞间交流的纳米囊泡。这些纳米囊泡在诸多疾病中发挥作用有一定的前提条件，取决于外来体来源的细胞类型。虽然很少的研究报道支气管肺泡灌洗液来源的外来体在哮喘进展中具有促炎作用，但肺组织内与外来体介导的相互作用相关的细胞类型以及其作用的转归尚未研究。
   目的：目前，已知外来体介导的细胞交流能影响疾病的表型。本研究旨在探索哮喘致病中外来体介导的结构性细胞和免疫细胞间的相互作用。
   方法：收集对照小鼠和哮喘小鼠的支气管肺泡灌洗液，并分离和检测外来体，采用磁珠分析进行定量。采用免疫组化检测肺组织涉及的上皮细胞和巨噬细胞。采用不同的在体和离体技术，研究IL-13在外来体产生中的作用。采用化学抑制剂在体和离体阻断外来体分泌，研究外来体对不同哮喘特征的影响。
   结果：通过联合在体和离体技术，我们发现，与对照组小鼠相比，哮喘小鼠肺组织内外来体分泌和外来体相关蛋白的产生增加。哮喘表现为，IL-13作用下上皮细胞（而非巨噬细胞）的外来体分泌增加。这些上皮细胞来源的外来体能诱导未分化巨噬细胞的增殖和趋化。另一方面，抑制外来体产生能显著减少增殖的单核细胞，缓解哮喘特征。
   结论：在哮喘炎症环境下，经IL-13作用后，上皮细胞来源的外来体能诱导肺内未分化的巨噬细胞增殖和趋化作用增加。                            
 

(林江涛 审校)
JAllergyClinImmunol. 2013Feb13.pii:S0091-6749(12)03565-8.doi:10.1016/j.jaci.2012.12.1565. [Epub ahead of print]
 

Proinflammatory role of epithelial cell-derived exosomes in allergic airway inflammation.
 
Kulshreshtha A, Ahmad T, Agrawal A, Ghosh B.

Source
Molecular Immunogenetics Laboratory and the Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.

Abstract
BACKGROUND: Exosomes are nanovesicles involved in intercellular communication. Their roles in various diseases are often contextual, depending on the cell type producing them. Although few studies hint toward the proinflammatory role of bronchoalveolar lavage fluid-derived exosomes in asthmatic progression, the cell types in lungs associated with exosome-mediated crosstalk and their resultant effects remain unexplored.
OBJECTIVE: It is well established that exosome-mediated cellular communication can influence disease phenotypes. This study explores exosome-mediated cellular crosstalk between structural and immune cells in asthma pathogenesis.
METHODS: Exosomes were isolated and detected from bronchoalveolar lavage fluid of control and asthmatic mice and were quantified by using a bead-based assay. Involvement of epithelial cells and macrophages were established by using immunohistochemical techniques in lung tissue sections. The role of IL-13 in exosome production was ascertained by using various in vitro and in vivo techniques. Exosome secretion was blocked in in vitro and in vivo settings by using a chemical inhibitor, and the effects on various asthmatic features were studied.
RESULTS: Using combinatorial in vitro and in vivo approaches, we found that exosome secretion and production of exosome-associated proteins are higher in lungs of asthmatic mice compared with that seen in sham mice. Asthma is marked by enhanced secretion of exosomes by epithelial cells, but not macrophages, under the influence of IL-13. These epithelial cell exosomes induce proliferation and chemotaxis of undifferentiated macrophages. On the other hand, GW4869, which inhibited exosome production, resulted in a reduced population of proliferating monocytes and alleviation of various asthmatic features.
CONCLUSION: Under the influence of IL-13, epithelial cell-derived exosomes can induce enhanced proliferation and chemotaxis of undifferentiated macrophages in the lungs during asthmatic inflammatory conditions.
 

JAllergyClinImmunol. 2013Feb13.pii:S0091-6749(12)03565-8.doi:10.1016/j.jaci.2012.12.1565. [Epub ahead of print]