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P2X7 RECEPTOR PLAYS A CRUCIAL ROLE IN LPS‐MEDIATED ACUTE LUNG INJURY
Author(s) -
Mishra Amarjit,
Weng Tingting,
Breshears Melanie,
Chintagari Narendranath R,
LIU LIN
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.111.3
Subject(s) - bronchoalveolar lavage , proinflammatory cytokine , lung , receptor , inflammation , purinergic receptor , medicine , cytokine , immunology , evans blue , pharmacology , endocrinology
Purinergic P2X 7 receptor is an ATP‐gated ion channel and participates in inflammation by regulating IL‐1β processing and release. Recent studies have identified the pathophysiological importance of P2X 7 receptor in immune and neuroinflammatory diseases. However, the role of P2X 7 receptor in acute lung injury is still unclear. In the present study using a two‐hit lung injury model of low dose endotoxin exposure and moderate tidal volume mechanical ventilation for 3 hours, we compared the early inflammatory response between wild‐type and P2X 7 −/− mice. There was a significant reduction in total bronchoalveolar lavage cell counts and neutrophil infiltration in lung tissue and lavage in P2X 7 −/− mice compared to wild‐type. Furthermore, myeloperoxidase from P2X 7 −/− mice lung homogenate was also reduced. The release of proinflammatory cytokine IL‐1β and IL‐6, but not TNF‐α from P2X 7 −/− mice showed a marked reduction. In parallel, transcripts of IL‐1β, IL‐6, and MCP‐1 from P2X 7 −/− mice failed to respond to challenge. However, TNF‐α, KC, and IL‐10 shows a similar expression pattern between wild‐type and P2X 7 −/− mice. Moreover, P2X 7 −/− mice exhibited less responsiveness to alveolar–capillary leakage, as measured by reduced bronchoalveolar lavage protein accumulation and Evans blue dye extravasion. Taken together our results support that P2X 7 receptor facilitates IL‐1β and IL‐6 release and is involved in the pathogenesis of acute lung injury.