Neutrophil F-actin Dynamics in Familial Mediterranean Fever: The Unequal Effect of Colchicine on Activated Neutrophils

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)


Volume 15, 3 Issues, 2016


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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Editor-in-Chief:
Claudiu T. Supuran
Neurofarba Department
University of Florence
Florence
Italy


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Neutrophil F-actin Dynamics in Familial Mediterranean Fever: The Unequal Effect of Colchicine on Activated Neutrophils



Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 12(2): 165-172.

Author(s): Tigran K. Davtyan, Samvel A. Avetisyan and Gagik S Hakobyan.

Affiliation: Laboratory of Immunology and Virology, "Armenicum" Research Centre, CJSC Armenicum, 37 Nalbandyan str., Yerevan 0001, Republic of Armenia.

Abstract

In the innate immune system, cellular adaptation regulates neutrophil activation and chemotaxis, which have a pivotal role in Familial Mediterranean Fever (FMF) pathogenesis. We investigated neutrophil F-actin, phagocytosis and macropinocytosis dynamics during neutrophil chemoattractant-dependent activation in FMF patients carrying mutations in the MEFV locus. We found that while a non-stimulated neutrophil shows an increased overall F-actin content in patients with FMF, the activation-dependent F-actin dynamics in the presence of chemoattractant peptide is significantly reduced. Neither overall F-actin content nor F-actin dynamics was changed in FMF patient’s neutrophils in the presence of double doses of chemoattractant, while in healthy donors it occurred with significant reduction of F-actin content and dynamics. The neutrophil shows increased phagocytosis and macropinocytosis dynamics for a relatively short period, which may contribute to the decreasing of plasticity of the cellular cytoskeleton during FMF. Colchicine causes reduction of overall F-actin content and shows a distinctively unequal effect on chemoattractant-activated neutrophil F-actin dynamics in FMF patients compared with healthy donors. These data suggested that mutations in MEFV cause the dissolution of cellular adaptation to chemoattractant stimuli due to alterations in neutrophil F-actin and phagocytosis dynamics, which could serve as a major target for FMF treatment.

Keywords:

Familial Mediterranean fever, neutrophil F-actin, phagocytosis, chemoattractant, colchicine.



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Article Details

Volume: 12
Issue Number: 2
First Page: 165
Last Page: 172
Page Count: 8
DOI: 10.2174/1871523011312020008
Price: $58
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