Platelet-leukocyte deregulated interactions foster sterile inflammation and tissue damage in immune-mediated vessel diseases.

Platelets and leukocytes co-localize and interact at sites of vessel injury, haemorrhage, thrombosis and inflammation. Recent studies have highlighted the role of local cues in the interaction between the two cell populations, including the exposure of anionic phospholipids and the release of Damage Associated Molecular Patterns (DAMPs) by activated platelets, the release of the prototypical tissue pentraxin PTX3 by neutrophils, as well as the generation of polarized clusters of neutrophil ß(2) integrins. In turn, the reciprocal activatory cross-talk between platelets and leukocytes contributes to the generation of thrombo-inflammatory lesions and of vascular injury.

The development of Ca2+ indicators: a breakthrough in pharmacological research.

The development, beginning in 1979, of fluorescent Ca2+-specific indicators as research tools has revolutionized transmembrane signaling studies. In this article, the state of the art in the 'pre-Ca2+-indicator' era and the rationale for the development of indicators trapped in the cytosol to investigate the cytosolic concentration of Ca2+ in mammalian cells are summarized. Subsequent extension of these studies to the level of the single cell, together with the unique impact that Ca2+ indicators have had on signaling research and the introduction of specific, fluorescent gene constructs that provide direct, high-resolution information about the intracellular concentration of Ca2+, are also discussed.