Open AccessCLIC1 null mice demonstrate a role for CLIC1 in macrophage superoxide production and tissue injury
Author(s) -
Ulmasov Barbara,
Bruno Jonathan,
Oshima Kiyoko,
Cheng YaoWen,
Holly Stephen P.,
Parise Leslie V.,
Egan Terrance M.,
Edwards John C.
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13169
Subject(s) - superoxide , nadph oxidase , reactive oxygen species , ezrin , microbiology and biotechnology , chemistry , intracellular , biology , cytoskeleton , biochemistry , cell , enzyme
We generated and studied CLIC 1 null (C1 KO ) mice to investigate the physiological role of this protein. C1 KO and matched wild‐type ( WT ) mice were studied in two models of acute toxic tissue injury. CLIC 1 expression is upregulated following acute injury of WT kidney and pancreas and is absent in C1 KO s. Acute tissue injury is attenuated in the C1 KO s and this correlates with an absence of the rise in tissue reactive oxygen species ( ROS ) that is seen in WT mice. Infiltration of injured tissue by inflammatory cells was comparable between WT and C1 KO s. Absence of CLIC 1 increased PMA ‐induced superoxide production by isolated peritoneal neutrophils but dramatically decreased PMA ‐induced superoxide production by peritoneal macrophages. CLIC 1 is expressed in both neutrophils and macrophages in a peripheral pattern consistent with either plasma membrane or the cortical cytoskeleton in resting cells and redistributes away from the periphery following PMA stimulation in both cell types. Absence of CLIC 1 had no effect on redistribution or dephosphorylation of Ezrin/ ERM cytoskeleton in macrophages. Plasma membrane chloride conductance is altered in the absence of CLIC 1, but not in a way that would be expected to block superoxide production. NADPH oxidase redistributes from an intracellular compartment to the plasma membrane when WT macrophages are stimulated to produce superoxide and this redistribution fails to occur in C1 KO macrophages. We conclude that the role of CLIC 1 in macrophage superoxide production is to support redistribution of NADPH oxidase to the plasma membrane, and not through major effects on ERM cytoskeleton or by acting as a plasma membrane chloride channel.