蜂窝样改变是一种与典型间质性肺炎(UIP)一致的组织学模式。蜂窝样改变是指囊状气道位于密集纤维化和明显粘液积聚的部位。利用激光捕获显微取样串联质谱(LCM-MS)，我们对来自10个UIP患者标本中的纤维性蜂窝气道细胞和纤维性未涉及气道细胞（远离蜂窝气道且形态完整）进行了研究。6名患者的非纤维化气道细胞标本作为对照。此外，我们对发现于6名UIP患者和6名粘液性腺癌患者的粘液栓进行了LCM-MS分析。质谱数据进行了定性和定量分析，并通过免疫组织化学验证。令人惊讶的是，纤维性未涉及的气道细胞与蜂窝样气道细胞具有相似的蛋白质表达谱，显示粘液调节路(Slit和Robo)径是最强的类别。我们发现，BPI折叠蛋白家族B成员1（BPIFB1）是UIP中最显著增加的分泌相关蛋白，而黏液素5AC (MUC5AC)在粘液性腺癌中最显著上调。我们得出结论，纤维性未涉及气道细胞与纤维性蜂窝气道细胞具有病理学特征相似。此外，纤维性蜂窝气道细胞富含粘液生物合成蛋白，并具有纤毛生成所必需的蛋白的显著破坏。这种无偏向性的空间蛋白质组学方法产生了新颖且可验证的假设，以解析纤维化进程。©2023。这是一项美国政府工作，不受美国版权保护法的保护，外国版权保护可能适用。

Honeycombing is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). Honeycombing refers to cystic airways located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic honeycomb airway cells and fibrotic uninvolved airway cells (distant from honeycomb airways and morphologically intact) in specimens from 10 patients with UIP. Non-fibrotic airway cell specimens from 6 patients served as controls. Furthermore, we performed LCM-MS on the mucus plugs found in 6 patients with UIP and 6 patients with mucinous adenocarcinoma. The mass spectrometry data were subject to both qualitative and quantitative analysis and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved airway cells share a similar protein profile to honeycomb airway cells, showing deregulation of the slit and roundabout receptor (Slit and Robo) pathway as the strongest category. We find that (BPI) fold-containing family B member 1 (BPIFB1) is the most significantly increased secretome-associated protein in UIP, whereas Mucin-5AC (MUC5AC) is the most significantly increased in mucinous adenocarcinoma. We conclude that fibrotic uninvolved airway cells share pathological features with fibrotic honeycomb airway cells. In addition, fibrotic honeycomb airway cells are enriched in mucin biogenesis proteins with a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach generates novel and testable hypotheses to decipher fibrosis progression.© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.