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Mitochondria Orchestrate Chemotaxis of Neutrophils by Fueling Their Autocrine Purinergic Signaling Systems
Author(s) -
Bao Yi,
Ledderose Carola,
Zhang Jingping,
Graf Amelie,
Chong Eritza,
Junger Wolfgang
Publication year - 2015
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.29.1_supplement.671.2
Subject(s) - autocrine signalling , purinergic receptor , chemotaxis , microbiology and biotechnology , purinergic signalling , mitochondrion , chemistry , signal transduction , biology , biochemistry , receptor , extracellular , adenosine receptor , agonist
Polymorphonuclear neutrophils (PMNs) need chemotaxis to find invading bacteria. We have previously demonstrated that chemotaxis depends on ATP release and autocrine purinergic signaling via P2Y2, A2a, and A3 receptors (Chen 2006, Bao 2013). Here we investigate the role of mitochondria in the production of the ATP that fuels these purinergic signaling mechanisms. Blocking mitochondria with CCCP, KCN, or oligomycin impaired ATP release from human PMNs following stimulation with the chemotactic bacterial peptide fMLP. CCCP also significantly impaired chemotaxis, abolishing gradient sensing as well as reducing migration speed in a chemotactic gradient field generated with a micropipette that was loaded with 100 nM fMLP (Fig. 1A). Addition of the non‐hydrolysable ATP analog ATPγS restored cell motility but was unable to restore gradient sensing. These findings indicate that localized purinergic signaling is required for proper PMN chemotaxis. We found two subsets of mitochondria in polarized PMNs (Fig. 1B). A small number of mitochondria with high membrane potential (Δψm) was found at the front (red) and the remaining mass of mitochondria with low Δψm stayed at the back (green) during chemotaxis. Our results suggest that mitochondria play an important role in regulating neutrophil chemotaxis by generating the ATP that fuels purinergic signaling. This study was supported by NIH grants R01 GM51477, R01 GM60475, R01 AI080582, and T32 GM103702.