Comparison of an automatic analysis and a manual analysis of conjunctival microcirculation in a sheep model of haemorrhagic shock

Life-threatening diseases of critically ill patients are known to derange microcirculation. Automatic analysis of microcirculation would provide a bedside diagnostic tool for microcirculatory disorders and allow immediate therapeutic decisions based upon microcirculation analysis

Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response

The innate immune response to bacterial infections requires the interaction of neutrophils and platelets. Here, we show that a multistep reciprocal crosstalk exists between these two cell types, ultimately facilitating neutrophil influx into the lung to eliminate infections. Activated platelets adhere to intravascular neutrophils through P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1)-mediated binding, a primary interaction that allows platelets glycoprotein Ib alpha (GPIb alpha)-induced generation of neutrophil-derived extracellular vesicles (EV). EV production is directed by exocytosis and allows shuttling of arachidonic acid into platelets. EVs are then specifically internalized into platelets in a Mac1-dependent fashion, and relocated into intracellular compartments enriched in cyclooxygenase1 (Cox1), an enzyme processing arachidonic acid to synthesize thromboxane A(2) (TxA(2)). Finally, platelet-derived-TxA(2) elicits a full neutrophil response by inducing the endothelial expression of ICAM-1, intravascular crawling, and extravasation. We conclude that critical substrate-enzyme pairs are compartmentalized in neutrophils and platelets during steady state limiting non-specific inflammation, but bacterial infection triggers regulated EV shuttling resulting in robust inflammation and pathogen clearance.The authors would like to thank Nadja Giesbrecht and Mareike Schluter for expert technical support. This work was supported by the Deutsche Forschungsgemeinschaft (ZA428/6-1 and ZA428/8-1 to A.Z., RO 4537/2-1 to J.R.) and Cells-in-Motion Cluster of Excellence EXC 1003-CiM (University of Munster, Germany; to A.Z.). Grant SAF2012-31142 from MINECO (to A.H.). Grant HL107386 from the NHLBI (to M.R.L.). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the MINECO and the Pro-CNIC Foundation.S

Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response

The innate immune response to bacterial infections requires the interaction of neutrophils and platelets. Here, we show that a multistep reciprocal crosstalk exists between these two cell types, ultimately facilitating neutrophil influx into the lung to eliminate infections. Activated platelets adhere to intravascular neutrophils through P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1)-mediated binding, a primary interaction that allows platelets glycoprotein Ib alpha (GPIb alpha)-induced generation of neutrophil-derived extracellular vesicles (EV). EV production is directed by exocytosis and allows shuttling of arachidonic acid into platelets. EVs are then specifically internalized into platelets in a Mac1-dependent fashion, and relocated into intracellular compartments enriched in cyclooxygenase1 (Cox1), an enzyme processing arachidonic acid to synthesize thromboxane A(2) (TxA(2)). Finally, platelet-derived-TxA(2) elicits a full neutrophil response by inducing the endothelial expression of ICAM-1, intravascular crawling, and extravasation. We conclude that critical substrate-enzyme pairs are compartmentalized in neutrophils and platelets during steady state limiting non-specific inflammation, but bacterial infection triggers regulated EV shuttling resulting in robust inflammation and pathogen clearance

Neutrophils Turn Plasma Proteins into Weapons against HIV-1

As a consequence of innate immune activation granulocytes and macrophages produce hypochlorite/hypochlorous acid (HOCl) via secretion of myeloperoxidase (MPO) to the outside of the cells, where HOCl immediately reacts with proteins. Most proteins that become altered by this system do not belong to the invading microorganism but to the host. While there is no doubt that the myeloperoxidase system is capable of directly inactivating HIV-1, we hypothesized that it may have an additional indirect mode of action. We show in this article that HOCl is able to chemically alter proteins and thus turn them into Idea-Ps (Idea-P = immune defence-altered protein), potent amyloid-like and SH-groups capturing antiviral weapons against HIV-1. HOCl-altered plasma proteins (Idea-PP) have the capacity to bind efficiently and with high affinity to the HIV-1 envelope protein gp120, and to its receptor CD4 as well as to the protein disulfide isomerase (PDI). Idea-PP was able to inhibit viral infection and replication in a cell culture system as shown by reduced number of infected cells and of syncytia, resulting in reduction of viral capsid protein p24 in the culture supernatant. The unmodified plasma protein fraction had no effect. HOCl-altered isolated proteins antithrombin III and human serum albumin, taken as representative examples of the whole pool of plasma proteins, were both able to exert the same activity of binding to gp120 and inhibition of viral proliferation. These data offer an opportunity to improve the understanding of the intricacies of host-pathogen interactions and allow the generation of the following hypothetical scheme: natural immune defense mechanisms generate by posttranslational modification of plasma proteins a potent virucidal weapon that immobilizes the virus as well as inhibits viral fusion and thus entry into the host cells. Furthermore simulation of this mechanism in vitro might provide an interesting new therapeutic approach against microorganisms

'Kids save lives': why schoolchildren should train in cardiopulmonary resuscitation

PURPOSE OF REVIEW Quick initiation of basic life support (BLS) by laypersons is one of the most successful strategies in the fight against sudden cardiac death. In developed countries, cardiac arrest is still a major contributor to avoidable death, and despite the fact that more than 50% of all cardiac arrests are witnessed, layperson BLS is performed in less than 20%. To improve this situation, BLS training in schools has been established. RECENT FINDINGS Cardiopulmonary resuscitation (CPR) instruction including the use of automatic external defibrillators (AEDs) has shown to be feasible even for young schoolchildren, and there is an indication that respective programmes are effective to enhance patient outcome on a population basis. Earlier training may even lead to more sustainable results; however, it is reasonable to implement adjusted curricula for different child ages. The programme 'Kids Save Lives' recently endorsed by the WHO will help promoting school-based BLS training worldwide demanding education on CPR for all pupils starting at least at age 12. SUMMARY Resuscitation training in schools can help to increase the amount of BLS-trained population. Social skills of pupils can be improved and training can be successfully implemented independently of the pupils' age and physique