Different particle determinants induce apoptosis and cytokine release in primary alveolar macrophage cultures

Particles are known to induce both cytokine release (MIP-2, TNF-alpha), a reduction in cell viability and an increased apoptosis in alveolar macrophages. To examine whether these responses are triggered by the same particle determinants, alveolar macrophages were exposed in vitro to mineral particles of different physical-chemical properties.

The crystalline particles of the different stone types mylonite, gabbro, basalt, feldspar, quartz, hornfels and fine grain syenite porphyr (porphyr), with a relatively equal size distribution (< or = 10 microm), but different chemical/mineral composition, all induced low and relatively similar levels of apoptosis. In contrast, mylonite and gabbro induced a marked MIP-2 response compared to the other particles. For particles of smaller size, quartz (< or = 2 microm) seemed to induce a somewhat stronger apoptotic response than even smaller quartz (< or = 0.5 microm) and larger quartz (< or = 10 microm) in relation to surface area, and was more potent than hornfels and porphyr (< or = 2 microm). The reduction in cell viability induced by quartz of the different sizes was roughly similar when adjusted to surface area. With respect to cytokines, the release was more marked after exposure to quartz < or = 0.5 microm than to quartz < or = 2 microm and < or = 10 microm. Furthermore, hornfels (< or = 2 microm) was more potent than the corresponding hornfels (< or = 10 microm) and quartz (< or = 2 microm) to induce cytokine responses. Pre-treatment of hornfels and quartz particles < or = 2 microm with aluminium lactate, to diminish the surface reactivity, did significantly reduce the MIP-2 response to hornfels. In contrast, the apoptotic responses to the particles were not affected.

These results indicate that different determinants of mineral/stone particles are critical for inducing cytokine responses, reduction in cell viability and apoptosis in alveolar macrophages. The data suggest that the particle surface reactivity was critical for cytokine responses, but contributed less to cell death for the types of particles tested. The size-dependent variations, specially in cytokine release, seem not to be explained only by particle surface area.