Inflammation is a key homeostatic process elicited by microbial components and by tissue damage. Increasing evidence indicates that the outcomes, either tissue repair or persistent inflammatory damage and degeneration, tightly depend on the pattern of cell death in situ and on the features of infiltrating leukocytes and antigen presenting cells that actually dispose of cell death remnants. Defects in the initiation and execution steps of programmed cell death such as in the clearance of cell debris are indeed very important for the pathogenesis of systemic autoimmune diseases, in which the deregulated response to cell death behaves both as an initiator and an amplifying circuit, leading to the specific features of each disease. In particular, during vascular inflammation a self-sustaining circuit attracts and activates inflammatory leukocytes in the wall of vessels of various size and anatomical characteristics. Vascular inflammation fulfils homeostatic roles and the activation of circulating leukocytes, platelets and endothelial cells is under the control of humoral innate immunity. We are directly addressing the molecular mechanisms underlying the vicious circle that maintains and amplifies vessel and tissue injury, with specific attention to the role of injury-associated signals (Damage-Associated Molecular Patterns, DAMPS, or Alarmins) and of acute phase proteins.