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Novel role of the transcriptional regulator HIF‐1α in the antimicrobial activity of mast cells
Author(s) -
KöckritzBlickwede Maren,
BranitzkiHeinemann Katja,
Okumura Cheryl,
Naim Hassan,
Nizet Victor
Publication year - 2011
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.25.1_supplement.562.11
Mast cells (MCs) are multifunctional immune cells that play a prominent role in a variety of important biological processes, including the host defence against bacterial pathogens. The detailed cellular signalling events mediating MC antimicrobial activities are still not completely understood. Here, we investigated the role of the transcription factor HIF‐1α. Treatment of human or murine MCs with a HIF‐1α agonist significantly increased antimicrobial activity against the pathogen Staphylococcus aureus . Corroborating this observation, treatment of cells with a HIF‐1α‐antagonist abolished this effect. Besides, HIF‐1α‐deficient MCs were significantly impaired in their antimicrobial activity, proofing the key role of HIF‐1α. Pharmacological treatment of the cells to block oxidative burst showed that HIF‐1α‐mediated killing by MCs is based on an oxidative mechanism that requires synthesis of ROS. Furthermore, we found that HIF‐1α mediates the release of antimicrobial histones H2A and H2B in association with extracellular DNA‐traps. MC antimicrobial activity was reduced by treating the cells with antibodies against histone‐DNA‐complexes. These data shed new light on the regulation of MC antimicrobial activity. The work was supported by NIH grant AI077780 to V.N., and by a fellowship from the Deutsche Akademie der Naturforscher Leopoldina (BMBF‐LPD 9901/8‐187) to M.v.K.B.