Participação da tripsina e do receptor ativado por protease (PAR)-4 no recrutamento de neutrófilos em modelo de pleurisia experimental

• Ano de defesa: 2012
• Autor(a) principal: Lindisley Ferreira Gomides
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Recrutamento de neutrófilos; Tripsina; Pleurisia; PAR-4; Carragenina; Neutrófilos; Fisiologia
• Link de acesso: http://hdl.handle.net/1843/BUOS-8WDHJP

Serine proteases act through the cleavage of the N-terminus cluster of G proteincoupled receptors known as PARs (proteinase activated receptors). After the cleavage, the remaining aminoacid chain acts like a ligand for its own receptors. Those receptors are classified from 1 to 4, and this classification depends on two factors: first, the cleavage spot in the N-terminal domain and second, on the serine protease responsible for the cleavage. PARs are expressed on a vast array of cells and are involved in various physiological mechanisms, being inflammation one ofthem. PAR-4 are expressed on leukocytes and their activation by trombin or trypsin seems to be involved with the activation of those cells, together with the proinflammatory phenomena induced by these proteases. However, the regulation process involved in the leukocytes recruitment to the inflammatory site in response to the serine proteases has not been elucidated. In this way, the trypsin participation on neutrophils recruitment to the pleural cavity of BALB/c mice in response to different inflammatory stimuli was investigated in this work, assessing the PAR-4 importancein the control of this process. Pre-treatment of the animals with aprotinin or with a PAR-4 selective antagonist, tcY-NH2, inhibited neutrophils migration induced by carrageenan or by trypsin, the neutrophils recruitment induced by trypsin equally inhibited after a treatment with a leucotrien(LT)B4 antagonist. Intrapleural administration of a PAR-4 activator peptide, LTB4, and interleucin (IL)-8 were also capable of inducing neutrophils recruitment to the pleural cavity. In conclusion, ourstudies demonstrate that PAR-4 activation plays an important role on the regulation of neutrophils recruitment in the pleurisy experimental model. Altogether, these results expand the knowledge of proteases participation in inflammatory response, thus suggesting a new strategic therapy to its control, through PARs-4 blockade/inhibition.