Cyclic hydrostatic pressure and cotton particles stimulate synthesis by human lung macrophages of cytokines in vitro

BACKGROUND Inhalation of particulates is a leading cause of the development of lung diseases and current understanding of the complex relationship between lung metabolism and airborne particulates is incomplete. It is well established that mechanical load is important in the development of the lung and in lung cell differentiation. The interaction between particle exposure and physical forces on alveolar macrophages is a physiologically relevant issue, but as yet understudied. This study examines the effect of cyclic hydrostatic pressure and cotton particles on synthesis of cytokines by human alveolar macrophages. METHODS Alveolar macrophages were obtained from patients with lung disease, either from lavage samples or from lung tissue resection. The commonly used cell line THP-1 was included in the experiments. Cell cultures were exposed to cotton particles and/cyclic hydrostatic pressure (3 or 5 psi); control cultures were exposed to medium only. TNFalpha, IL-1beta and IL-6 were assayed in the culture media using specific ELISAs. Cells were characterized using morphology and markers specific for macrophages (Jenner/Giemsa staining, CD14 and CD68). RESULTS Exposure to cotton particles stimulated cytokine synthesis by macrophages from all three sources; exposure to cyclic hydrostatic pressure alone did not stimulate cytokine synthesis significantly. However, the combination of both particles and cyclic hydrostatic pressure increased the simulation of cytokine synthesis still further. Cell characterization demonstrated that the large majority of cells had a macrophage morphology and were positive for CD14 and CD68. CONCLUSION These data suggest an interaction between cyclic hydrostatic pressure and particulate exposure, which increases alveolar macrophage cytokine production. This interaction was only observed at the higher cyclic hydrostatic pressure. However, in patient samples, there was considerable variation in the amount by which secretion of an individual cytokine increased and there was also variation in the mechanosensitivity of cells from the three different sources. Cyclic hydrostatic pressure, therefore, may be an important modulator of the response of alveolar macrophages to cotton particles, but the source of the cells may be a confounding factor which demands further investigation.