Polyamines as regulators of pulmonary inflammation

<bold>Background</bold>. Polyamines are polycationic molecules found in all cells and tissues. Inflamed lung is known to contain elevated concentrations of extracellular polyamines, which were shown to exert a modulatory action on the local immune response and the virulence of harmful pathogens. However, it remains unclear which pulmonary cell type contributes to the extracellular polyamine release, and how polyamines affect innate immunity. <bold>Objective</bold>. To study the interplay of inflammation and polyamine signalling in an <italic>in vitro</italic> model of pulmonary inflammation. <bold>Methods and Results</bold>. Human pulmonary cells such as pneumocytes (type 1 and 2), pulmonary microvascular endothelial cells (PMVECs), A549 cells, and lung fibroblasts were cultured <italic>in vitro</italic>. Circulating blood polymorphonuclear cells, >95% neutrophils, were obtained from healthy donors. The cells were tested for release of the polyamine, spermine. PMVECs displayed the highest efficiency reaching >0.7 ng/ml following 24 hours in culture (n=3-5). Lipopolysaccharide-induced polyamine production by PMVECs was significantly augmented in hypoxic, but not normoxic, conditions. Exogenous application of spermine affected viability of PMVECs and neutrophils but not pneumocytes or A549 cells. Spermine did not alter release of pro-inflammatory cytokines, such as tumour necrosis factor alpha and interleukin-1 beta, from PMVECs, pneumocytes, or A549 cells. However, spermine stimulated neutrophil transmigration and upregulated phagocytosis and <italic>Staphylococcus aureus</italic> clearance in a dose-dependent manner. <bold>Conclusions</bold>. Polyamines released from pulmonary endothelium during inflammation and hypoxia may stimulate activity of circulating neutrophils to facilitate transmigration and pathogen clearance in the lung.