Marta Camprubí-Rimblas

An Overview of Proteomics on Sepsis

Over the last years, proteomics has provided us a lot of information about the spectrum of all the proteins that are expressed by an organism in pathological and non-pathological processes. The advantage of studying the proteome over other omics (genomics, epigenetics, transcriptomics and metabolomics) is that proteins reflect the final effectors in all the complex network of replication, transcription and translation. Sepsis is a systemic inflammatory response caused by infection and that could produce multiple organ dysfunctions. The study of the secreted proteins would improve the knowledge of molecular mechanisms and pathways implicated in the septic process and consequently, data will allow us to find new therapeutic targets. The objective of this review is to summarize the proteomics updates of preclinical and clinical studies of sepsis in fields like pathophysiology, treatment, diagnosis or prognosis, providing new perspectives and directions of sepsis. Proteomics is a useful technique for the understanding of the pathophysiology of sepsis infection, the identification of new molecules for an early diagnosis and the prognosis, and the follow-up of treatment progress. The validation of new biomarkers needs a large cohort of patients and the use of other additional methods. Nevertheless, together with other techniques, proteomics has added important elements to the understanding of sepsis and other diseases. Despite current limitations, proteomic techniques improvement with bioinformatics tools might help results interpretation. Besides, the bettering in sensitivity and sensibility may facilitate further sepsis studies with these techniques.

Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury

Objective  Alveolar macrophages play a key role in the development and resolution of acute respiratory distress syndrome (ARDS), modulating the inflammatory response and the coagulation cascade in lungs. Anti-coagulants may be helpful in the treatment of ARDS. This study investigated the effects of nebulized heparin on the role of alveolar macrophages in limiting lung coagulation and inflammatory response in an animal model of acute lung injury (ALI). Methods  Rats were randomized to four experimental groups. In three groups, ALI was induced by intratracheal instillation of lipopolysaccharide (LPS) and heparin was nebulized at constant oxygen flow: the LPS/Hep group received nebulized heparin 4 and 8 hours after injury; the Hep/LPS/Hep group received nebulized heparin 30 minutes before and 4 and 8 hours after LPS-induced injury; the LPS/Sal group received nebulized saline 4 and 8 hours after injury. The control group received only saline. Animals were exsanguinated 24 hours after LPS instillation. Lung tissue, bronchoalveolar lavage fluid (BALF) and alveolar macrophages isolated from BALF were analysed. Results  LPS increased protein concentration, oedema and neutrophils in BALF as well as procoagulant and proinflammatory mediators in lung tissue and alveolar macrophages. In lung tissue, nebulized heparin attenuated ALI through decreasing procoagulant (tissue factor, thrombin–anti-thrombin complexes, fibrin degradation products) and proinflammatory (interleukin 6, tumour necrosis factor alpha) pathways. In alveolar macrophages, nebulized heparin reduced expression of procoagulant genes and the effectors of transforming growth factor beta (Smad 2, Smad 3) and nuclear factor kappa B (p-selectin, CCL-2). Pre-treatment resulted in more pronounced attenuation. Conclusion  Nebulized heparin reduced pulmonary coagulopathy and inflammation without producing systemic bleeding, partly by modulating alveolar macrophages.

Intratracheal instillation of alveolar type II cells enhances recovery from acute lung injury in rats

BACKGROUND Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by excess production of inflammatory factors. Alveolar type II (ATII) cells help repair damaged lung tissue, rapidly proliferating and differentiating into alveolar type I cells after epithelial cell injury. In ALI, the lack of viable ATII favors progression to more severe lung injury. ATII cells regulate the immune response by synthesizing surfactant and other anti-inflammatory proteins and lipids. Cross-talk between ATII and other cells such as macrophages may also be part of the ATII function. The aim of this study was to test the anti-inflammatory and reparative effects of ATII cells in an experimental model of ALI. METHODS In this study ATII cells (2.5 × 106 cells/animal) were intratracheally instilled in rats with HCl and lipopolysaccharide (LPS)-induced ALI and in healthy animals to check for side effects. The specific effect of ATII cells was compared with fibroblast transplantation. RESULTS ATII cell transplantation promoted recovery of lung function, decrease mortality and lung inflammation of the animals with ALI. The primary mechanisms for benefit were paracrine effects of prostaglandin E2 (PGE2) and surfactant protein A (SPA) released from ATII cells that modulate alveolar macrophages to an anti-inflammatory phenotype. To our knowledge, these data are the first to provide evidence that ATII cells secrete PGE2 and SPA, reducing pro-inflammatory macrophage activation and ALI. CONCLUSION ATII cells and their secreted molecules have shown an ability to resolve ALI, thereby highlighting a potential novel therapeutic target.