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Chronic plasminogen activator inhibitor‐1 (PAI‐1) overexpression dampens CD25+ lymphocyte recruitment after lipopolysaccharide endotoxemia in mouse lung
Author(s) -
POGGI M.,
PAULMYERLACROIX O.,
VERDIER M.,
PEIRETTI F.,
BASTELICA D.,
BOUCRAUT J.,
LIJNEN H. R.,
JUHANVAGUE I.,
ALESSI M. C.
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02757.x
Subject(s) - plasminogen activator , lipopolysaccharide , plasminogen activator inhibitor 1 , inflammation , spleen , foxp3 , fibrin , sepsis , immunology , il 2 receptor , lymphocyte , lung , cytokine , chemistry , biology , medicine , endocrinology , immune system , t cell
Summary. Background: Plasma plasminogen activator inhibitor‐1 (PAI‐1) level rises during sepsis and confers a worse prognosis. PAI‐1 participation to sepsis has been poorly documented and was mainly associated with fibrin deposits. Beside fibrin deposits, increased tissue PAI‐1 expression may contribute to the poor outcome of endotoxemia through other mechanisms. Objective and methods: During lipopolysaccharide (LPS) challenge, the role of PAI‐1 in the early phase of inflammation was examined in the lungs of transgenic mice that either overexpress or lack the PAI‐1 gene (PAI‐1Tg or PAI‐1 −/− ). Results: Analysis of leukocytes revealed that neutrophil and macrophage infiltrations did not differ for PAI‐1Tg and wild‐type (WT) mice. Remarkably, CD25+ lymphocyte infiltration was totally blunted in PAI‐1Tg lungs and inversely correlated with fibrin depositions. In parallel, mRNA levels of the regulatory T cell (Treg) markers FoxP3, CTLA‐4, and GITR were significantly lower in PAI‐1Tg than in WT lungs after LPS challenge. These data are supported by opposite results in PAI‐1 −/− lungs. The systemic compartments (spleen and peripheral blood) showed no decrease in CD25+, CD4+ CD25+ lymphocytes, and Treg markers in PAI‐1Tg mice after LPS injection compared with WT mice. In addition, plasma and lung concentrations of interleukin‐6 (IL‐6) and macrophage inflammatory protein‐1α (MIP‐1α) were significantly higher in PAI‐1Tg mice than WT mice. Conclusion: Our results suggest that chronic tissue PAI‐1 overexpression influences the early phase of the inflammatory response during endotoxemia through the control of T lymphocyte traffic.