Dual Effect of Neutrophils on pIgRSecretory Component in Human Bronchial Epithelial Cells : Role of TGF-β

Abstract EN

Neutrophils have a dual affect on epithelial pIgR/SC, the critical receptor for transcellular routing of mucosal IgA, but mechanisms of pIgR/SC upregulation remain elusive.

Requirements of cytokine, redox, and signalling pathways for pIgR/SC production were assessed in human bronchial epithelial (Calu-3) cells cocultured with increasing numbers of blood neutrophils.

Increased SC production was observed after incubation for 48 hrs with intermediate neutrophil numbers (1.25 to 2.5×106), was favoured by the elastase inhibitor SLPI, and correlated with increased TGF-β production.

Exogenous TGF-β stimulated SC production with a maximal effect at 48 hrs and both TGF-β- and neutrophil-driven SC upregulation were dependent on redox balance and p38 MAP-kinase activation.

This paper shows that activated neutrophils could upregulate epithelial pIgR/SC production through TGF-β-mediated activation of a redox-sensitive and p38 MAPK-dependent pathway.

An imbalance between the two neutrophil-driven opposite mechanisms (SC upregulation and SC degradation) could lead to downregulation of pIgR/SC, as observed in severe COPD.