PDT-induced HSP70 externalization up-regulates NO production via TLR2 signal pathway in macrophages.

We studied the molecular mechanism underlying PDT-induced apoptosis-dependent macrophage activation, particularly through NO production. We demonstrate that NO production is initially induced by HSP70 on the apoptotic cell surface, and is further enhanced by macrophage phagocytosis. Additionally, we found that apoptotic cells, through TLR2, could activate PI3K, and this could be either dependent or independent of the activation of MyD88. These results reveal a novel pathway linking innate immune signalling to apoptotic cells and point at HSP70 as an important antitumor immunostimulant. They also indicate that PDT-induced apoptosis has an important role in macrophage innate immunity.