SRF is required for neutrophil migration in response to inflammation.

Abstract:

:Serum response factor (SRF) is a ubiquitously expressed transcription factor and master regulator of the actin cytoskeleton. We have previously shown that SRF is essential for megakaryocyte maturation and platelet formation and function. Here we elucidate the role of SRF in neutrophils, the primary defense against infections. To study the effect of SRF loss in neutrophils, we crossed Srf(fl/fl) mice with select Cre-expressing mice and studied neutrophil function in vitro and in vivo. Despite normal neutrophil numbers, neutrophil function is severely impaired in Srf knockout (KO) neutrophils. Srf KO neutrophils fail to polymerize globular actin to filamentous actin in response to N-formyl-methionine-leucine-phenylalanine, resulting in significantly disrupted cytoskeletal remodeling. Srf KO neutrophils fail to migrate to sites of inflammation in vivo and along chemokine gradients in vitro. Polarization in response to cytokine stimuli is absent and Srf KO neutrophils show markedly reduced adhesion. Integrins play an essential role in cellular adhesion, and although integrin expression levels are maintained with loss of SRF, integrin activation and trafficking are disrupted. Migration and cellular adhesion are essential for normal cell function, but also for malignant processes such as metastasis, underscoring an essential function for SRF and its pathway in health and disease.

journal_name

Blood

journal_title

Blood

authors

Taylor A,Tang W,Bruscia EM,Zhang PX,Lin A,Gaines P,Wu D,Halene S

doi

10.1182/blood-2013-06-507582

subject

Has Abstract

pub_date

2014-05-08 00:00:00

pages

3027-36

issue

19

eissn

0006-4971

issn

1528-0020

pii

blood-2013-06-507582

journal_volume

123

pub_type

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