Faculty Collaboration Database

Kindlin-3 negatively regulates the release of neutrophil extracellular traps. J Leukoc Biol 2018 Sep;104(3):597-602

Date

04/16/2018

Pubmed ID

29656482

Pubmed Central ID

PMC6113072

DOI

10.1002/JLB.3AB0118-005R

Scopus ID

2-s2.0-85045414281 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

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.

Author List

Xu Z, Ni B, Cao Z, Zielonka J, Gao J, Chen F, Kalyanaraman B, White GC, Ma YQ

Authors

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
Gilbert C. White MD Professor in the Medicine department at Medical College of Wisconsin
Jacek M. Zielonka PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cytoskeletal Proteins
Extracellular Traps
HL-60 Cells
Humans
Inflammation
Membrane Proteins
Mice
Mice, Knockout
Neoplasm Proteins
Neutrophils
Signal Transduction