Bradykinin inducible receptor is essential to lipopolysaccharide-induced acute lung injury in mice

Author(s)

Campanholle, Gabriela ^[1] ; Landgraf, Richardt G. ^[2] ; Borducchi, Erica ^[3] ; Semedo, Patricia ^[4] ; Wang, Pamela H. M. ^[4] ; Amano, Mariane T. ^[1] ; Russo, Momtchilo ^[3] ; Pacheco-Silva, Alvaro ^[4] ; Jancar, Sonia ^[5] ; Camara, Niels O. S. ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Lab Transplantat Immunobiol, Dept Immunol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Immunol, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Clin & Expt Immunol Lab, Div Nephrol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Lab Immunopharmacol, Dept Immunol, Sao Paulo - Brazil

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 634, n. 1-3, p. 132-137, MAY 25 2010.
• Web of Science Citations: 10

Abstract

Lipopolysaccharides from gram-negative bacteria are amongst the most common causative agents of acute lung injury, which is characterized by an inflammatory response, with cellular infiltration and the release of mediators/cytokines. There is evidence that bradykinin plays a role in lung inflammation in asthma but in other types of lung inflammation its role is less clear. In the present study we evaluated the role of the bradykinin B(1) receptor in acute lung injury caused by lipopolysaccharide inhalation and the mechanisms behind bradykinin actions participating in the inflammatory response. We found that in C57BI/6 mice, the bradykinin B(1) receptor expression was up-regulated 24 h after lipopolysaccharide inhalation. At this time, the number of cells and protein concentration were significantly increased in the bronchoalveolar lavage fluid and the mice developed airway hyperreactivity to methacholine. In addition, there was an increased expression of tumor necrosis factor-alpha, interleukin-1 beta and interferon-gamma and chemokines (monocytes chemotactic protein-1 and KC) in the bronchoalveolar lavage fluid and in the lung tissue. We then treated the mice with a bradykinin B, receptor antagonist, R-954 (Ac-Orn-{[}Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8)]desArg(9)-bradykinin), 30 min after lipopolysaccharide administration. We observed that this treatment prevented the airway hyperreactivity as well as the increased cellular infiltration and protein content in the bronchoalveolar lavage fluid. Moreover, R-954 inhibited the expression of cytokines/chemokines. These results implicate bradykinin, acting through B(1) receptor, in the development of acute lung injury caused by lipopolysaccharide inhalation. (C) 2010 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 06/03982-5 - Molecular aspects involved in leukocytes microbicidal and inflammatory activities in the lung
• Grantee: Sônia Jancar
• Support Opportunities: Research Projects - Thematic Grants