Extracellular nucleic acids as novel alarm signals in the vascular system. Mediators of defence and disease.

Upon vascular injury or tissue damage, the exposed intracellular material such as nucleic acids, histones and other macromolecules may come into contact with vessel wall cells and circulating blood cells and may thus, have an enduring influence on wound healing and body defence processes. This short review summarizes recent work related to extracellular DNA and RNA and their role as prominent alarm signals and inducers of different defence reactions related to innate immunity and thrombus formation. Of particular importance are DNA-histone complexes (nucleosome material) that, having been expelled during stimulation of the neutrophils, not only trap and eliminate bacteria but also promote thrombus formation in the arterial and venous system. Consequently therefore, the administration of DNase exhibits strong antithrombotic functions. Similarly, extracellular RNA provokes activation of the contact phase system of blood coagulation and, by interacting with specific proteins and cytokines, it promotes vascular permeability and oedema formation. The development of RNA-mediated thrombosis, vasogenic oedema or proinflammatory responses are counteracted by the administration of RNase1 in several pathogenetic animal models. Thus, extracellular nucleic acids appear not only to function as host alarm signals that serve to amplify the defence response, but they also provide important links to thrombus formation as part of the innate immune system.