Publication:
Focal adhesion kinase regulates pathogen-killing capability and life span of neutrophils via mediating both adhesion-dependent and -independent cellular signals

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Issued Date

2009

Resource Type

Article

File Type

application/pdf

ISSN

221767

DOI

10.4049/jimmunol.0802984

Other identifier(s)

2-s2.0-70249095029

Rights Holder(s)

Scopus

Bibliographic Citation

Journal of Immunology. Vol 183, No.2 (2009), p.1032-1043

Suggested Citation

Kasorn A., Alcaide P., Jia Y., Subramanian K.K., Sarraj B., Li Y., Loison F., Hattori H., Silberstein L.E., Luscinskas W.F., Luo H.R. Focal adhesion kinase regulates pathogen-killing capability and life span of neutrophils via mediating both adhesion-dependent and -independent cellular signals. Journal of Immunology. Vol 183, No.2 (2009), p.1032-1043. doi:10.4049/jimmunol.0802984 Retrieved from: https://hdl.handle.net/20.500.14740/5960

Title

Focal adhesion kinase regulates pathogen-killing capability and life span of neutrophils via mediating both adhesion-dependent and -independent cellular signals

Author(s)

Kasorn A.
 Alcaide P.
 Jia Y.
 Subramanian K.K.
 Sarraj B.
 Li Y.
 Loison F.
 Hattori H.
 Silberstein L.E.
 Luscinskas W.F.
 Luo H.R.

Abstract

Various neutrophil functions such as phagocytosis, superoxide production, and survival are regulated by integrin signaling. Despite the essential role of focal adhesion kinase (FAK) in mediating this signaling pathway, its exact function in neutrophils is ill defined. In this study, we investigated the role of FAK in neutrophils using a myeloid-specific conditional FAK knockout mouse. As reported in many other cell types, FAK is required for regulation of focal adhesion dynamics when neutrophils adhere to fibronectin or ICAM-1. Adhesion on VCAM-1-coated surfaces and chemotaxis after adhesion were not altered in FAK null neutrophils. In addition, we observed significant reduction in NADPH oxidase-mediated superoxide production and complementmediated phagocytosis in FAK null neutrophils. As a result, these neutrophils displayed decreased pathogen killing capability both in vitro and in vivo in a mouse peritonitis model. In adherent cells, the defects associated with FAK deficiency are likely due to suppression of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) signaling and chemoattractant-elicited calcium signaling. Disruption of FAK also reduced chemoattractant-elicited superoxide production in suspended neutrophils in the absence of cell adhesion. This may be solely caused by suppression of PtdIns(3,4,5)P3 signaling in these cells, because the fMLP-elicited calcium signal was not altered. Consistent with decreased PtdIns(3,4,5)P3/Akt signaling in FAK null neutrophils, we also observed accelerated spontaneous death in these cells. Taken together, our results revealed previously unrecognized roles of FAK in neutrophil function and provided a potential therapeutic target for treatment of a variety of infectious and inflammatory diseases. Copyright © 2009 by The American Association of Immunologists, Inc.

Subject(s)

Chemoattractant
 Complement
 Fibronectin
 Focal adhesion kinase
 Intercellular adhesion molecule 1
 Protein kinase B
 Reduced nicotinamide adenine dinucleotide phosphate oxidase
 Superoxide
 Vascular cell adhesion molecule 1
 Cell adhesion molecule
 Focal adhesion kinase
 Phosphatidylinositol 3,4,5 trisphosphate
 Phosphatidylinositol 3,4,5-triphosphate
 Polyphosphoinositide
 Animal cell
 Animal experiment
 Animal model
 Article
 Cell adhesion
 Cell death
 Cell surface
 Cell survival
 Cell suspension
 Chemotaxis
 Controlled study
 Focal adhesion
 In vitro study
 In vivo study
 Intracellular signaling
 Mouse
 Neutrophil
 Nonhuman
 Null allele
 Pathogenicity
 Peritonitis
 Phagocytosis
 Priority journal
 Animal
 Calcium signaling
 Cytology
 Immunology
 Metabolism
 Mouse mutant
 Phagocytosis
 Physiology
 Signal transduction
 Animals
 Calcium Signaling
 Cell Adhesion
 Cell Adhesion Molecules
 Cell Death
 Chemotaxis
 Focal Adhesion Protein-Tyrosine Kinases
 Mice
 Mice, Knockout
 Neutrophils
 Peritonitis
 Phagocytosis
 Phosphatidylinositol Phosphates
 Signal Transduction

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URI

https://hdl.handle.net/20.500.14740/5960

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Scopus: Year 1983-2021

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