New directions in inflammation and immunity: the multi-functional role of the extracellular RNA/RNase system.

In the mid-eighties of the last century, extracellular-proteolipid complexes have been identified in tumor patients and circulating RNA was suggested to represent a specific secretory product of cancer cells. The presence of specific types of RNA in a variety of cancer types proved to be useful in cancer diagnosis. It has been suggested that extracellular RNA and DNA are not inert molecules, but contain biological activities. Recent data have demonstrated that extracellular RNA is likely to present the up to now undefined "natural foreign surface", serving as an initiating factor in blood coagulation in vivo. Yet, extracellular RNA seems to have even more functions. Investigations on blood-brain-barrier have shown that extracellular RNA mediates endothelial permeability. Ample success has been achieved in administrating RNase in different animal models of vascular diseases, thereby significantly delaying thrombus formation and reducing cerebral edema formation with neuroprotection in acute stroke models. Furthermore, extracellular mammalian RNA was found to decrease tumor yield in a murine model system, suggesting that extracellular RNA might trigger immune response. Finally, extracellular nucleic acids were identified as danger signals involved in innate immunity related to neutrophil-mediated bacterial killing and haemocyte activation and coagulation in the insects. Thus, a new area of research on extracellular RNA functions with promising future perspectives just started in the field of inflammation and immunity.