Altered progenitor cell and cytokine profiles in bronchiolitis obliterans syndrome

Abstract

Bone marrow-derived progenitor cells may play a key role in both lung repair and in fibrogenesis. The contribution of CD45(+)collagen-1(+) fibrocytes to fibrosis has been documented elsewhere and recently identified epithelial-like progenitor cells marked by Clara cell secretory protein (CCSP(+)) may be protective after lung injury. Interplay between these populations has not yet been studied in bronchiolitis obliterans syndrome (BOS) post-lung transplant. In a cross-sectional design, blood samples were analyzed for CCSP(+) cells and CD45(+)collagen-1(+) fibrocytes by flow cytometry. Plasma cytokines were analyzed by multiplex array. A higher proportion of circulating fibrocytes was measured in patients with BOS Grade ≥1 than in those with BOS Grade 0(p). In parallel, a lower proportion of CCSP(+) cells was found in BOS ≥1 patients compared with BOS 0(p) and non-transplant controls, resulting in an altered cell ratio between the groups. A higher ratio of CD45(+)collagen-1(+) to CCSP(+) cells was associated with greater airflow limitation based on FEV(1) and FEV(1)/FVC ratio. No relationship between cell profiles and time post-transplant was found. Plasma analysis showed an increase in key stem cell and inflammatory cytokines in both groups post-transplant, whereas stromal-derived factor-1 and vascular endothelial growth factor were increased in cases of BOS ≥1 specifically. Plasma stromal-derived factor-1 levels also correlated with fibrocytes post-transplant. Overall, altered progenitor cell profiles were found in patients who developed advanced BOS, which may be mediated by alterations in circulating cytokines. Ultimately, measurement of progenitor cell profiles may lead to further insight into the pathogenesis of airflow obstruction after lung transplantation.