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

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

Journal Name: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Formerly Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents

Volume 12 , Issue 2 , 2013

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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

Year: 2013
Page: [165 - 172]
Pages: 8
DOI: 10.2174/1871523011312020008
Price: $65

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