Oncostatin M is produced by neutrophils, and promotes epithelial barrier dysfunction in mucosal airways disease

Abstract

Abstract We have previously shown that Oncostatin M (OSM) was elevated in nasal polyp (NP) tissue from chronic rhinosinusitis (CRS) patients, and in BAL fluid following segmental allergen challenge (SAC) in allergic asthmatics (AA). Levels of OSM detected in vivo were sufficient to impair epithelial barrier function in ex vivo cultured airway epithelium. To determine which cell type(s) was producing OSM, NP sections were stained for OSM and hematopoietic cell specific markers. OSM showed co-localization with neutrophil elastase(n=10), but not with markers for eosinophils, macrophages, T cells or B cells (n=3–5). OSM mRNA correlated with mRNA for neutrophil markers CD16 (r=.61, p<.01) and cathepsin G (r=.56, p<.01) in mRNA from CRS patients and controls. OSM also correlated with the percent neutrophils in the BAL of AA following SAC (r=.50, p<.05), but did not correlate with total cell counts or eosinophil counts. Flow cytometric analysis of cells isolated from NP (n=10) showed that 14±6% of CD45+ cells were OSM+, and 85±6% of OSM+ cells were CD16+Siglec 8-, indicating neutrophil lineage. GM-CSF and FSTL-1 have been shown to induce OSM, and both were found to be elevated in NP. Additionally, GM-CSF, alone or in combination with FSTL-1, was sufficient to induce both OSM mRNA in ex vivo cultured blood neutrophils and OSM protein in the culture supernatants. These data suggest that neutrophils are the major producers of OSM in NP, and may potentially mediate epithelial barrier dysfunction in mucosal airways disease.