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Extracellular ATP induces IL‐1beta secretion and formation of filopodia in myeloid lineage cells through distinct P2X7‐dependent pathways
Author(s) -
Thomas Louis Michael,
Chu Jessica,
Watkins Simon C.,
Stolz Donna,
Salter Russell D.
Publication year - 2008
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.22.1_supplement.672.21
Subject(s) - microbiology and biotechnology , purinergic receptor , extracellular , secretion , filopodia , biology , signal transduction , microvesicles , chemistry , actin , biochemistry , microrna , gene
Extracellular ATP (ATPe) is an endogenous danger signal which acts as a ligand for purinergic receptors on immune cells, resulting in complex changes in cytokine production, migration, function, and morphology. We have identified cytoskeletal changes in macrophages and dendritic cells (DC) induced by ATPe acting on P2X 7 , an ion channel purinergic receptor, that result in formation of unbranched non‐substrate attached filopodia (AIF) that frequently fragment into microvesicles. We investigated whether these structures represent a source of inflammatory cytokines including IL‐1beta, whose release is known to be induced by ATPe via P2X 7 activation. Pharmacologic and genetic manipulations to probe both IL‐1beta secretion and AIF formation demonstrated that the pathways controlling these two processes are distinct. AIF formation requires actin polymerization and PLD activity while being insensitive to inhibition of pannexin and caspase‐1 function. In contrast, IL‐1beta secretion is not blocked by inhibitors of PLD, but does require caspase‐1 and pannexin activity. These results show that extracellular ATP induces a complex response in myeloid cells involving multiple signaling pathways.