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- W2317145800 abstract "Exudate macrophages are key players in host defense towards invading pathogens. Their anti-inflammatory and epithelial-protective potential in gram-negative pneumonia, however, remains elusive. Objective: We investigated whether exudate macrophages contributed to preservation of alveolar epithelial barrier integrity and analyzed the molecular pathways involved. Methods: We evaluated the anti-inflammatory and epithelial-protective effects of exudate macrophages in a model of LPS- and K. pneumoniae-induced lung injury comparing wild-type and CCR2 (CC-chemokine receptor 2)-deficient mice with defective lung macrophage recruitment and in in vitro studies using primary alveolar epithelial cells. CCR2–/– mice exhibited enhanced alveolar epithelial cell apoptosis and lung leakage upon intratracheal LPS treatment which could be attributed to lack of exudate macrophage recruitment from the circulating pool as demonstrated in a model of wild-type/CCR2–/– bone-marrow chimeric mice. Among various anti-inflammatory and proliferative mediators analysed, the endogenous counterpart of resident macrophage-expressed interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra), was highly upregulated in flow-sorted exudate macrophages in LPS-treated wild-type mice. LPS/IL-1β-induced impairment of alveolar epithelial cell integrity was antagonized by IL-1ra in vitro. Finally, intratracheal substitution of IL-1ra or intravenous adoptive transfer of IL-1ra+/+ but not IL-1ra–/– blood mononuclear cells attenuated alveolar inflammation, epithelial apoptosis, and loss of barrier function in LPS-challenged or K. pneumoniae-infected CCR2–/– mice and enhanced survival after K. pneumoniae infection. We conclude that recruited lung macrophages attenuate IL-1β-mediated acute lung injury in gram-negative pneumonia by release of IL-1ra." @default.
- W2317145800 created "2016-06-24" @default.
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- W2317145800 date "2011-03-01" @default.
- W2317145800 modified "2023-10-17" @default.
- W2317145800 title "Exudate macrophages attenuate lung injury by the release of IL-1 receptor antagonist in gram-negative pneumonia" @default.
- W2317145800 doi "https://doi.org/10.1055/s-0031-1272254" @default.
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