Neutrophil F-actin Dynamics in Familial Mediterranean Fever: The Unequal Effect of Colchicine on Activated Neutrophils
Tigran K. Davtyan,
Samvel A. Avetisyan,
Gagik S. Hakobyan.
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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