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Kindlin‐3 negatively regulates the release of neutrophil extracellular traps
Author(s) -
Xu Zhen,
Ni Beiwen,
Cao Zhongyuan,
Zielonka Jacek,
Gao Juan,
Chen Fangyuan,
Kalyanaraman Balaraman,
White Gilbert C.,
Ma YanQing
Publication year - 2018
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.3ab0118-005r
Subject(s) - neutrophil extracellular traps , microbiology and biotechnology , gene knockdown , biology , integrin , inflammation , haematopoiesis , reactive oxygen species , immunology , receptor , apoptosis , stem cell , biochemistry
Neutrophils fight infections by generating reactive oxygen species (ROS) and extracellular traps (NETs). However, how neutrophils modulate ROS/NET generation is mechanistically unclear. Kindlin‐3, an essential integrin activator expressed in hematopoietic cells, is required to support integrin‐mediated neutrophil recruitment during inflammation. Here, we report a novel role of kindlin‐3 in regulating ROS/NET generation in neutrophils. When overexpressing kindlin‐3 in neutrophil‐like differentiated HL‐60 cells (HL‐60N), ROS/NET generation from these cells were significantly suppressed. Interestingly, overexpression of a kindlin‐3 mutant that is defective for interacting with integrins in HL‐60N cells still inhibited ROS/NET generation, suggesting that the role of kindlin‐3 in inhibiting ROS/NET signaling may be independent of its binding to integrins. Consistently, knockdown of kindlin‐3 in HL‐60N cells led to enhanced ROS/NET generation. In addition, bone marrow neutrophils isolated from kindlin‐3‐deficient mice showed elevated ROS/NET generation when compared with WT counterparts. As expected, overexpression of exogenous kindlin‐3 in mouse neutrophils could suppress NET release ex vivo and in vivo . Collectively, these results demonstrate that kindlin‐3 in neutrophils is involved in modulating the ROS/NET signaling, providing a novel mechanism for fine‐tuning neutrophil behaviors during inflammation.