Dual effect of neutrophils on secretory component production by human bronchial epithelial cells

Abstract

A decreased bronchial expression of secretory component (SC) was demonstrated in severe COPD, and correlated with neutrophils. Mechanisms of epithelial cell/neutrophils interactions remain however poorly understood. Calu-3 (human bronchial epithelial) cells were incubated after confluence (in triplicate conditions) with various ratios of activated neutrophils (0.5:1 to 15:1, neutrophils: Calu-3 cells). After 48hrs of co-culture supernatants were assayed for SC by ELISA. SC production by Calu-3 cells increased at intermediate neutrophil numbers (316±32 versus 193±19ng·ml–1, ratio of 5:1 versus control, mean±SEM of 3 experiments, p = 0.05). In contrast, a trend for decrease in SC was observed with high neutrophil numbers (111±19 versus 193±19ng·ml–1, ratio of 15:1 versus control, p = 0.06). The addition of secretory leukocyte protease inhibitor further increased SC upregulation at intermediate ratios, and inhibited the SC decrease at high neutrophil numbers. The mechanism of SC up-regulation by neutrophils did not implicate TNF-alpha or IL-1beta. This study provides direct evidence of a dual effect of neutrophils on epithelial SC. Our data suggest that neutrophils could differently affect epithelial immune secretory function according to the extent of neutrophil influx and/or to the reactivity of airway epithelial cells.