PAFR and ICAM-1 expression increases in patients with IPF: implications for microbial pathogenesis

<bold>Introduction:</bold> Idiopathic pulmonary fibrosis (IPF) is an irreversible lung disorder of unknown cause. Bacterial and viral co-infections exacerbate pathogenesis, using adhesion molecules like platelet activating factor receptor (PAFR) and intercellular adhesion molecule 1 (ICAM-1) for cellular entry, causing infections. This study compares PAFR and ICAM-1 expression in IPF patients' small airways and lung parenchyma with normal lungs and COVID-19-related marker (ACE2) expression, exploring if IPF patients are more susceptible to infections. <bold>Methods:</bold> Surgically resected lung tissue from 11 IPF patients and 12 normal controls (NC) were immunohistochemically stained for PAFR, ICAM-1 and ACE2. Positive expression percentages of each marker in the small airway epithelium and the lung parenchymal area were assessed. All image analysis was done using Image Pro Plus 7 software. <bold>Results:</bold> Compared to NC, IPF patients had significantly higher levels of PAFR expression in the small airway epithelium (p<0.0001), type 2 pneumocytes (p<0.05) and alveolar macrophages (p<0.05). Similarly, elevated ICAM-1 levels were observed in IPF patients in the epithelium (p<0.0001), type 2 pneumocytes (p<0.0001) and alveolar macrophages (p<0.0001) compared to NC. Furthermore, ACE2 expression was significantly increased in the epithelium (p<0.01) and in lung parenchyma (p<0.001) of IPF patients compared to NC. ICAM-1 surpassed ACE2 and PAFR expression in IPF. <bold>Conclusion:</bold> This study is the first evaluation of PAFR and ICAM-1 expression in small airway epithelium, type 2 pneumonocytes and alveolar macrophages in IPF, and compared to ACE2. These insights could help mitigate microbial impact and manage disease progression.