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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Editor-in-Chief

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

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

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

Volume 12, Issue 2, 2013

Page: [165 - 172] Pages: 8

DOI: 10.2174/1871523011312020008

Price: $65

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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