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Activation of Neutrophils (PMNs) Adherent to Endothelial Cells (ECs) Signals Ca2+ Entry via the Redox‐Sensitive TRPM2 Ca2+ Channel
Author(s) -
Ahmmed Gias Uddin,
Gao Xiao Pei,
Malik Asrar B
Publication year - 2007
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.21.5.a447-d
Subject(s) - trpm2 , nadph oxidase , chemistry , thapsigargin , superoxide , respiratory burst , adhesion , biophysics , stimulation , superoxide dismutase , microbiology and biotechnology , transient receptor potential channel , biochemistry , reactive oxygen species , intracellular , receptor , oxidative stress , enzyme , biology , endocrinology , organic chemistry
PMN adhesion to ECs may promote the activation of ECs; thus, we addressed the role of TRPM2 channel in ECs in inducing PMN‐mediated activation of ECs. We used the PMN‐specific agonist fMLP to stimulate PMNs interacting with ECs. Human pulmonary artery ECs were loaded with the Ca 2+ indicator Fura‐2, which was followed by addition of freshly isolated PMN stimulated by 1μM fMLP. We observed a rapid increase in [Ca 2+ ] i in ECs following PMN activation. Stimulation of ECs with thapsigargin to inhibit store‐operated Ca 2+ channels partly reduced the Ca 2+ entry. Blocking PMN adhesion by anti‐CD18 mAb and or anti‐ICAM‐1 mAb prevented the increase [Ca 2+ ] i in ECs. Pretreatments of ECs with superoxide dismutase, catalase, or DPI (NADPH oxidase) also prevented the increase in [Ca 2+ ] i . We observed that siRNA‐mediated suppression of TRPM2 expression blocked the Ca 2+ entry and over‐expression of TRPM2 augmented increase in [Ca 2+ ] i . These results suggest that PMN adhesion to ECs promotes Ca 2+ entry via redox‐sensitive TRPM2 channels. Thus, PMN generation of oxidants and resulting activation of TRPM2 Ca 2+ channels may be an important mechanism of EC injury.