Please use this identifier to cite or link to this item: https://ir.swu.ac.th/jspui/handle/123456789/15054
ชื่อเรื่อง: Focal adhesion kinase regulates pathogen-killing capability and life span of neutrophils via mediating both adhesion-dependent and -independent cellular signals
ผู้แต่ง: 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.
Keywords: 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
วันที่เผยแพร่: 2009
บทคัดย่อ: 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.
URI: https://ir.swu.ac.th/jspui/handle/123456789/15054
https://www.scopus.com/inward/record.uri?eid=2-s2.0-70249095029&doi=10.4049%2fjimmunol.0802984&partnerID=40&md5=6c4fe8571237d9261b6dc74c0b50f88d
ISSN: 221767
Appears in Collections:Scopus 1983-2021

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