Two Chromogranin A-Derived Peptides Induce Calcium Entry in Human Neutrophils by Calmodulin-Regulated Calcium Independent Phospholipase A2

Background: Antimicrobial peptides derived from the natural processing of chromogranin A (CgA) are co-secreted with catecholamines upon stimulation of chromaffin cells. Since PMNs play a central role in innate immunity, we examine responses by PMNs following stimulation by two antimicrobial CgA-derived peptides. Methodology/Principal Findings: PMNs were treated with different concentrations of CgA-derived peptides in presence of several drugs. Calcium mobilization was observed by using flow cytometry and calcium imaging experiments. Immunocytochemistry and confocal microscopy have shown the intracellular localization of the peptides. The calmodulin-binding and iPLA2 activating properties of the peptides were shown by Surface Plasmon Resonance and iPLA2 activity assays. Finally, a proteomic analysis of the material released after PMNs treatment with CgA-derived peptides was performed by using HPLC and Nano-LC MS-MS. By using flow cytometry we first observed that after 15 s, in presence of extracellular calcium, Chromofungin (CHR) or Catestatin (CAT) induce a concentration-dependent transient increase of intracellular calcium. In contrast, in absence of extra cellular calcium the peptides are unable to induce calcium depletion from the stores after 10 minutes exposure. Treatment with 2-APB (2-aminoethoxydiphenyl borate), a store operated channels (SOCs) blocker, inhibits completely the calcium entry, as shown by calcium imaging. We also showed that they activate iPLA2 as the two CaM-binding factors (W7 and CMZ) and that the two sequences can be aligned with the two CaMbinding domains reported for iPLA2. We finally analyzed by HPLC and Nano-LC MS-MS the material released by PMNs following stimulation by CHR and CAT. We characterized several factors important for inflammation and innate immunity. Conclusions/Significance: For the first time, we demonstrate that CHR and CAT, penetrate into PMNs, inducing extracellular calcium entry by a CaM-regulated iPLA2 pathway. Our study highlights the role of two CgA-derived peptides in the active communication between neuroendocrine and immune systems

The Joint Influence of Intra- and Inter-Team Learning Processes on Team Performance: A Constructive or Destructive Combination?

In order for teams to build a shared conception of their task, team learning is crucial. Benefits of intra-team learning have been demonstrated in numerous studies. However, teams do not operate in a vacuum, and interact with their environment to execute their tasks. Our knowledge of the added value of inter-team learning (team learning with external parties) is limited. Do both types of team learning compete over limited resources, or do they form a synergistic combination? We aim to shed light on the interplay between intra- and inter-team learning in relation to team performance, by including adaptive and transformative sub-processes of intra-team learning. A quantitative field study was conducted among 108 university teacher teams. The joint influence of intra- and inter-team learning as well as structural (task interdependence) and cultural (team efficacy) team characteristics on self-perceived and externally rated team performance were explored in a path model. The results showed that adaptive intra-team learning positively influenced self-perceived team performance, while transformative intra-team learning positively influenced externally rated team performance. Moreover, intra-team and inter-team learning were found to be both a constructive and a destructive combination. Adaptive intra-team learning combined with inter-team learning led to increased team performance, while transformative intra-team learning combined with inter-team learning hurt team performance. The findings demonstrate the importance of distinguishing between both the scope (intra- vs. inter-team) and the level (adaptive vs. transformative) of team learning in understanding team performance