IL-8 response of cyclically stretching alveolar epithelial cells exposed to non-fibrous particles

Using a cell stretcher device, we have previously shown that A549 cells exposed to asbestos fibers gave significantly increased cytokine responses (IL-8) when they were cyclically stretched [Tsuda, A., B. K. Stringer, S. M. Mijailovich, R. A. Rogers, K. Hamada, and M. L. Gray. Am. J. Respir. Cell Mol. Biol. 21(4):455-462, 1999]. In the present study, cell stretching experiments were performed using non-fibrous riebeckite particles, instead of fibrous particles. Riebeckite particles are ground asbestos fibers with the size of a few microns and non-fibrous shape, and are often used as "non-toxic" control particles in the studies of fibrous particle-induced pathogenesis. Although it is generally assumed that riebeckite particles do not elicit strong biological responses, in our studies in cyclically stretched cell cultures, the riebeckite particles coated with adhesion proteins induced significant IL-8 responses, but in static cell cultures the treatment with adhesion protein-coated riebeckite did not induce comparable cytokine responses. To interpret these data, we have developed a simple mathematical model of adhesive interactions between a cell layer and rigid fibrous/non-fibrous particles that were subjected to external tensile forces. The analysis showed that because of considerable dissimilarity in deformations (i.e., strain mismatch) between the cells and particles during breathing, the attachment of particles as small as 1 micro in size could induce significant mechanical forces on the cell surface receptors, which may trigger subsequent adverse cell response under dynamic stretching conditions.