Microparticles from apoptotic platelets promote resident macrophage differentiation

Platelets shed microparticles not only upon activation, but also upon ageing by an apoptosis-like process (apoptosis-induced platelet microparticles, PMap). While the activation-induced microparticles have widely been studied, not much is known about the (patho)physiological consequences of PMap formation. Flow cytometry and scanning electron microscopy demonstrated that PMap display activated integrins and interact to form microparticle aggregates. PMap were chemotactic for monocytic cells, bound to these cells, an furthermore stimulated cell adhesion and spreading on a fibronectin surface. After prolonged incubation, PMap promoted cell differentiation, but inhibited proliferation. Monocyte membrane receptor analysis revealed increased expression levels of CD11b (integrin αMβ2), CD14 and CD31 (platelet endothelial cell adhesion molecule-1), and the chemokine receptors CCR5 and CXCR4, but not of CCR2. This indicated that PMap polarized the cells into resident M2 monocytes. Cells treated with PMap actively consumed oxidized low-density lipoprotein (oxLDL), and released matrix metalloproteinases and hydrogen peroxide. Further confirmation for the differentiation towards resident professional phagocytes came from the finding that PMap stimulated the expression of the (ox)LDL receptors, CD36 and CD68, and the production of proinflammatory and immunomodulating cytokines by monocytes. In conclusion, interaction of PMap with monocytic cells has an immunomodulating potential. The apoptotic microparticles polarize the cells into a resident M2 subset, and induce differentiation to resident professional phagocytes

Trauma- und Gewaltfolgen – psychische Auswirkungen

This paper addresses consequences of exposure to violence and trauma. Traumata are defined as events with an extraordinary threat or catastrophic extent. Beside Posttraumatic Stress Disorder (PTSD), affected people may develop Complex PTSD, Prolonged Grief Disorder or Adjustment Disorder as direct consequences of exposure with extreme stress. Indirect trauma-related disorders are amongst others Major Depression, Substance Dependency and Personality Disorders. These disorders develop often comorbid to PTSD. The likelihood to develop a PTSD at one point during the life course is 1-4 % in Germany. A PTSD is diagnosed if for any length of time the traumatic situation is re-experienced (e.g. in pictures or nightmares), potential triggers are avoided, emotional reactivity is numb and a permanent hyperarousal is experienced. The intensity, the duration and the frequency of traumatic experiences as well as the lack of social support after the trauma are important risk factors for the development of a PTSD. In the last two decades successful treatment approaches for PTSD have been developed. The main focus of all evidence-based treatment approaches is the exposure in sensu of the traumatic experiences. Behavioral therapy approaches have shown to be most effective in the treatment of PTSD. A better understanding of the consequences of exposure to violence and trauma may help us to identify people at risk for developing trauma-related disorders already at an early stage