Investigation of the mechanisms of acute lung injury, using an isolated perfused mouse lung

Acute lung injury (ALI) is a severe inflammatory lung disease with high mortality. Previous studies revealed several important concepts in ALI, including cellular interaction between lung-marginated leukocytes and pulmonary endothelium, and decompartmentalisation of soluble mediators. However, there are inherent limitations within both in vivo and in vitro models to identify the detailed mechanism underlying these concepts. In this PhD project, we attempted to address these unanswered questions, using an in situ isolated perfused mouse lung (IPL). Specifically, we aimed to 1) develop, characterise, and optimise the mouse IPL model; 2) investigate soluble and cellular aspects of two models of ALI that are particularly amenable to study using the IPL, namely ventilator-induced lung injury (VILI) and ischaemia-reperfusion injury. From a physiological viewpoint, VILI consists of 2 primary components, high-stretch and atelectasis. Modelling atelectasis-related injury in vivo is difficult due to negative pleural pressure. We took advantage of the zero pleural pressure of open-chest IPL system to develop an atelectasis-related VILI model. Comparison of this ‘atelectrauma’ and a high-stretch ‘volutrauma’ model demonstrated that both cause lung oedema and pulmonary inflammation, but the inflammatory impact was different between them. Volutrauma, but not atelectrauma, facilitated systemic cytokine release, in which lung-marginated monocytes seem to play an important role. This finding in the VILI model drove us to further investigate the role of these monocytes in an ischaemia-reperfusion model, which is clinically highly relevant and simulates a lung transplantation setting. Our results suggested that lung-marginated monocytes may also contribute to develop ischaemia-reperfusion injury, potentially involving TNF upregulation. Through this PhD project, we have successfully developed a technically very challenging mouse IPL model. We utilised the unique features of the IPL to develop experimental models that we believe will be strong tools to fill the gap between in vivo physiological significance and in vitro mechanistic understanding

The Application of Viruses to Biotechnology

Viruses are microscopic agents that exist worldwide and are present in humans, animals, plants, and other living organisms in which they can cause devastating diseases. However, the advances of biotechnology and next-generation sequencing technologies have accelerated novel virus discovery, identification, sequencing, and manipulation, showing that they present unique characteristics that place them as valuable tools for a wide variety of biotechnological applications. Many applications of viruses have been used for agricultural purposes, namely concerning plant breeding and plant protection. Nevertheless, it is interesting to mention that plants have also many advantages to be used in vaccine production, such as the low cost and low risks they entail, showing once more the versatility of the use of viruses in biotechnology. Although it will obviously never be ignored that viruses are responsible for devastating diseases, it is clear that the more they are studied, the more possibilities they offer to us. They are now on the front line of the most revolutionizing techniques in several fields, providing advances that would not be possible without their existence. In this book there are presented studies that demonstrate the work developed using viruses in biotechnology. These studies were brought by experts that focus on the development and applications of many viruses in several fields, such as agriculture, the pharmaceutical industry, and medicine

Treatment of Later Humoral Rejection with Anti-CD20 Monoclonal Antibody Rituximab: A Single Centre Experience

Humoral or vascular rejection is a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ that results in immune complex deposition on the vascular endothelium, activation of the complement cascade, production of endothelial dysfunction and regional ischaemic injury