期刊
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
卷 179, 期 2-3, 页码 314-325出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.resp.2011.09.015
关键词
Lipopolysaccharide; Purinergic receptors; Acute lung injury; Inflammation
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil (CNPq)
- Instituto Nacional para Pesquisa Translacional em Saude e Ambiente na Regiao Amazonica (INCT-INPeTAm/CNPq/MCT)
- Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Programa de Apoio a Nucleos de Excelencia (PRONEX), Brazil
Rationale: P2X7 receptors have been involved in inflammatory and immunological responses, and their activation modulates pro-inflammatory cytokines production by LPS-challenged macrophages. Objectives: To determine the role of P2X7R in LPS-induced acute lung injury in mice. Methods: Wild-type (C57BL/6) and P2X7 knockout mice received intratracheal injection of saline or Escherichia coli LPS (60 mu g). After 24 h, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage was performed, and lungs were harvested for measurement of morphometry, fibers content, inflammatory cells and cytokine expression by histochemistry and immunohistochemistry. Results: Compared with saline, LPS increased lung mechanical parameters, mast cell, collagen and fibronectin deposition in lung parenchyma, as well as nitric oxide and lactate dehydrogenase release into bronchoalveolar fluid in wild-type, but not in P2X7R knockout mice. Alveolar collapse, lung influx of polymorphonuclear and CD14(+) cells, as well as TGF-beta, MMP-2, and IL-1 beta release were higher in wildtype than knockout LPS-challenged mice, while MMP-9 release where similar between the two genotypes. LPS increased macrophage immunoreactivity in lung tissue in both genotypes, but macrophages were not activated in the P2X7R knockout mice. Furthermore, LPS administration increased P2X7R immunoexpression in lung parenchyma in wild-type mice, and TLR4 in both wild-type and P2X7R knockout mice. Conclusion: P2X7 receptors are implicated in the pathophysiology of LPS-induced lung injury, modulating lung inflammatory and functional changes. (C) 2011 Elsevier B.V. All rights reserved.
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