| Grant number: | 05/02271-5 |
| Support type: | Regular Research Grants |
| Duration: | April 01, 2006 - June 30, 2008 |
| Field of knowledge: | Biological Sciences - Pharmacology - General Pharmacology |
| Principal Investigator: | Wothan Tavares de Lima |
| Grantee: | Wothan Tavares de Lima |
| Home Institution: | Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
Abstract
The intestinal ischemia and reperfusion injury (intestinal-I/R) is a clinical problem associated with systemic inflammation, pulmonary microcirculation dysfunction and Acute Respiratory Distress Syndrome (ARDS). ARDS is a form of acute pulmonary injury characterized by tissue and microvascular injury. Although neutrophils exert a pivotal role in this disorder, a definitive pharmacological approach to ARDS treatment is yet unavailable probably due the complexity of mechanisms involved to pulmonary inflammation. The generation of mediators and growth factors, which interact with the endothelial cells, constitute a crucial event for the lung injury. On the other hand, its relevance to repair process was still not yet explored. Recently we showed that the magnitude of the inflammation and the pulmonary microvascular injury caused by the intestinal-I/R is modulated by factors drained from lymph of the mesenteric system. Factors of lymph could affect the endothelial-leukocyte interaction, causing generation of new inflammatory mediators in the lung and modifying the functional state of pulmonary phagocytes. In this study primary cultures of endothelial cells will be established and kept in contact with neutrophils of I/R-intestinal rats. In parallel, the effects of lymph from animals submitted to intestinal-I/R on endothelial-leukocyte interaction will also investigated. Finally, the components of the endothelial cells, the extracellular matrix and the enzymes involved in the degradation of this matrix will be evaluated. At the same time, the effect of the intestinal-I/R after longer periods of reperfusion (1, 3 and 5 days) on the pulmonary injury and the regulating mechanisms of the pulmonary tecidual repair will be analyzed. (AU)