Objectives To examine neutrophil actin cytoskeleton dynamics during neutrophil chemoattractant-dependent activation in patients with Familial Mediterranean Fever (FMF), in an effort to understand the mechanisms that regulate switch of neutrophil activation program and therapeutic effect of colchicine (Col).
Methods Whole blood neutrophils obtained from 37 FMF patients and 15 healthy donors, without MEFV mutations (ND), were activated with chemoattractant peptide N-formyl-Met-Leu-Phe (FMLP), and cellular F-actin content determined by flow cytometry before and after exposure to Col.
Results 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 FMLP are significantly reduced. 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.
Conclusions Impaired neutrophil F-actin cytoskeleton dynamics that tightly regulate switch of neutrophil activation program during its encounter with chemoattractants might be a potential pathogenic mechanism causing aberrant resolution of inflammation and could represent a potential target for Col therapy during FMF. MEFV-mutated neutrophils showed a unique sensitivity to Col, which causes the re-organization of the actin cytoskeleton with a reduction of overall F-actin.
Disclosure of Interest : None declared