Pathophysiologic significance of procoagulant microvesicles in cancer disease and progression.

Microvesicles (MV) are submicrometric membrane fragments (0.1 to 1 microm), released from the plasma membrane of activated or apoptotic cells. They are characterized by most of the antigenic profile of the cells they originate from, and by the presence of procoagulant phospholipids at their surface. MV are detectable in the peripheral blood of mammals and considered as efficient effectors in the haemostatic or thrombotic responses, able to remotely initiate or amplify beneficial or deleterious processes, depending on the circumstances. Variations in their level and phenotype make them relevant pathogenic markers of thrombotic disorders and vascular damage. To date, MV are recognized as mediators of communication allowing cells to influence a target present in the local microenvironment as well as to at distant sites. The mechanisms by which MV interact with target cells are still unclear, but a number of studies suggest involvement of MV-cell fusion or ligand-receptor interactions. More importantly, MV have been shown implicated in horizontal transfer of genetic material. This review focuses on the role of MV in the context of cancer, and their possible part in cancer associated thrombosis.

Autoantibodies from Sjögren's syndrome induce activation of both the intrinsic and extrinsic apoptotic pathways in human salivary gland cell line A-253.

Sjögren's syndrome (SS) is an autoimmune rheumatic disease that targets salivary and lachrymal glands, characterized by a high concentration of serum autoantibodies directed against nuclear and cytoplasmic antigens. It is known that autoantibodies can enter viable cells and this phenomenon has functional consequences including activation of apoptotic process. The objective of this work was to explore whether autoantibodies contained in IgG purified from Sjögren sera trigger apoptotic process in an experimental model represented by the human salivary gland cell line A-253. To define if the intrinsic or extrinsic pathways are activated, we examined which caspases are critical for inducing cell death. The results have demonstrated that morphological changes and DNA laddering, consistent with apoptotic cell death, occurred in A-253 cells treated with IgG from Sjögren sera. Sjögren IgG induced cleavage and activation of the effector caspase-3 and degradation of the caspase-3 substrate poly(ADP-ribose)polymerase. Both the intrinsic and extrinsic apoptotic pathways were activated, since both caspase-8 and caspase-9 cleavages occurred. In conclusion, autoantibodies contained in IgG purified from Sjögren sera mediate apoptosis of the A-253 cell line in a caspase-dependent manner.