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Mechanisms underlying endothelial-leukocyte interaction after gut trauma and their relevance to acute lung injury: regulatory role of the lymphatic system

Grant number: 05/02271-5
Support Opportunities: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
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


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)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BREITHAUPT-FALOPPA, ANA CRISTINA; VITORETTI, LUANA BEATRIZ; CAVRIANI, GABRIELA; LINO-DOS-SANTOS-FRANCO, ADRIANA; SUDO-HAYASHI, LIA SIGUEMI; OLIVEIRA-FILHO, RICARDO MARTINS; BORIS VARGAFTIG, B.; TAVARES-DE-LIMA, WOTHAN. Intestinal Lymph-Borne Factors Induce Lung Release of Inflammatory Mediators and Expression of Adhesion Molecules After an Intestinal Ischemic Insult. JOURNAL OF SURGICAL RESEARCH, v. 176, n. 1, p. 195-201, . (07/07139-3, 05/02271-5)

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