The flavonoid galangin induces release of neutrophil extracellular traps and enhances resolution of E. coli pneumonia
Killing of invading bacteria is essential for efficient control of infection and return to homeostasis. Phagocytosis of E. coli by neutrophils induces neutrophil apoptosis and subsequent efferocytosis, critical control points of the outcome of inflammation. Recently, we found that E. coli DNA impair...
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| Published in: | The Journal of immunology (1950) Vol. 198; no. 1_Supplement; pp. 148 - 148.6 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
01-05-2017
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| Online Access: | Get full text |
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| Summary: | Killing of invading bacteria is essential for efficient control of infection and return to homeostasis. Phagocytosis of E. coli by neutrophils induces neutrophil apoptosis and subsequent efferocytosis, critical control points of the outcome of inflammation. Recently, we found that E. coli DNA impairs phagocytosis of E. coli by human neutrophils, delays neutrophil apoptosis and prolongs E. coli-evoked lung injury in mice. Here, we investigated whether the flavonoid galangin, which was shown to exert anti-inflammatory actions in several inflammation models, could also affect neutrophil function and the outcome of bacterial infection. In human neutrophils, galangin (100μM) did not affect viability or apoptosis; it efficiently countered the potent apoptosis-delaying cue from E. coli DNA by decreasing activation of ERK 1/2 and Akt, leading to Mcl-1 degradation and to collapse of mitochondrial trans-membrane potential. Galangin alone did not affect phagocytosis of live E. coli by neutrophils, and did not restore diminished phagocytosis in the presence of E. coli DNA. Consequently, phagocytosis-mediated bacterial killing was unaffected. By contrast, galangin triggered release of neutrophil extracellular traps (NETs). This was associated with enhanced bacterial killing, which was prevented in the presence of DNAse-I. In mice, galangin administered at the peak of inflammation, accelerated clearance of bacteria and the resolution of pulmonary injury evoked by intratracheal instillation of live E. coli. Collectively, these results identify novel mechanism, overriding survival cues from E. coli DNA and inducing release of NETs, by which galangin could facilitate bacterial clearance and the resolution of inflammation. |
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| ISSN: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.198.Supp.148.6 |