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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