Dynamic Neutrophil Subsets and Function in Lung Transplant Recipients: Insights from a One-Year Longitudinal Pilot Study

Background: Neutrophils are key innate immune cells in peripheral blood. In recent years, sub-populations of neutrophils have been identified. In addition to the normal-density neutrophils (NDNs) in both healthy subjects and patients, low-density neutrophils (LDNs) were described in chronic inflammation and cancer. In lung transplants (LTx), neutrophils play crucial roles in reperfusion injury, acute rejection, and chronic lung allograft dysfunction. Our pilot study examines neutrophil subsets and function in LTx recipients during the first post-transplant year. Methods: We collected blood from 11 LTx recipients at various intervals. LDNs and normal-density neutrophils (NDNs) were isolated. The production of reactive oxygen species (ROS) by NDNs was measured after PMA activation using a Luminol-HRP assay. Neutrophil phenotypic markers were analyzed with flow cytometry. Results: The LDN-to-NDN ratio increased at 3 and 6 months post-transplant. Expression levels of CD62-L (aging marker), PDL-1 (immune checkpoint), CD15 (maturation), and CXCR4 (homeostasis regulator) showed modulation. Interestingly, ROS production by NDNs was mildly elevated at baseline, reduced at 6 months, and returned to baseline levels by 9 months post-transplant. Conclusions: Neutrophils exhibit dynamic changes in the first post-LTx year. Investigating neutrophil plasticity could reveal clinically relevant biomarkers and facilitate the development of diagnostic and therapeutic tools in LTx.