Premium
Mitochondria determine TNFα receptor distribution in lung microvessels
Author(s) -
Rowlands David John,
Lindert Jens,
Bhattacharya Jahar
Publication year - 2009
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.23.1_supplement.594.20
Subject(s) - mitochondrion , tumor necrosis factor alpha , proinflammatory cytokine , chemistry , receptor , microbiology and biotechnology , inflammation , confocal , pathology , biology , endocrinology , immunology , medicine , biochemistry , geometry , mathematics
Circulating tumor necrosis factor alpha (TNFα) ligates endothelial (EC) TNFα receptor 1 (TNFR1) to promote inflammation. Although mitochondria are capable of proinflammatory signaling in lung EC (Ichimura, JCI 2003), the mitochondrial role in TNFα‐mediated inflammation remains unknown. To determine mitochondria‐TNFR1 relationships, we viewed ECs of single microvessels in isolated, blood‐perfused rat lungs by live confocal microscopy. To determine spatial expressions of EC mitochondria and TNFR1 by fluorescence quantification, we infused microvessels respectively, with the mitochondria‐specific fluorophore, mitotracker green (MTG), or a fluorophore‐conjugated, anti‐TNFR1 mAb. Buffer microinjections removed unbound dye. Microvascular expressions for both mitochondria and TNFR1 were 3‐fold higher at venular branch points than at septal capillaries (p<0.05, n=4). Fluorescence determinations along the microvascular length indicated that mitochondria and TNFR1 fluorescence intensities correlated at venular branch points (p<0.05 by linear regression), but not in septal capillaries. These findings are the first evidence that in lung microvessels, TNFR1 localizes to mitochondria‐rich regions. Mitochondrial mechanisms may regulate TNFR1‐induced inflammatory responses.