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Annexin A1 and neutrophils: mechanisms involved in gestation, Melanoma metastasis and Intestinal Ulcerative Disease

Abstract

Our research group has shown the role of neutrophils and the protein annexin A1 (AnxA1) in different processes of aggression in the organism. In this context, we show that neutrophils and AnxA1 are fundamental for blastocyst implantation and for maternal tolerance during the pregnancy; AnxA1 secreted by neutrophils may be involved in the pulmonary metastasis of melanoma; and that AnxA1 is essential for the action of drugs used for the treatment of colitis. Thus, this project aims to deepen the mechanisms of action of neutrophils and AnxA1 regarding: 1) blastocyst implantation and placenta formation, as well as the evolution of full-term pregnancy and the developing fetus using animals pharmacologically depleted of neutrophils; 2) the metastasis of melanoma in animals depleted for neutrophils, as well as correlating with the profile of neutrophils and AnxA1 in blood and samples obtained from patients at different stages of melanoma; 3) the composition of the gut microbiota in the absence and presence of experimental colitis in AnxA1-deficient or wild-type animals. Flow cytometry, histology and immunofluorescence assays will be used for tissue analysis obtained in different experimental approaches, quantification of gene and protein expressions, and chemical mediator dosages by ELISA and gene sequencing. The project has the collaboration of national and international researchers and graduate students, and will be carried out at the Faculty of Pharmaceutical Sciences at USP. The results obtained will contribute to the understanding of the role of the innate system in key points of the organism in the aggressions of different natures, thus contributing to several fronts of knowledge. It is worth mentioning that we have made great advances in studies on AnxA1, which allow the design of this project, in a thematic project financed by FAPESP in 2014 (2014/07328-4). (AU)

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